Molecular mechanisms in T helper phenotype development

Abbas AK, Murphy KM, Sher A (1996) Functional diversity of helper T lymphocytes. Nature 383:787Google Scholar

Adachi O, Kawai T, Takeda K, Matsumoto M, Tsutsui H, Sakagami M, Nakanishi K, Akira S (1998) Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity 9:143Google Scholar

Agarwal S, Rao A (1998) Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. Immunity 9:765Google Scholar

Ahmad S, Alsayed YM, Druker BJ, Platanias LC (1997) The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein. J Biol Chem 272:29991Google Scholar

Altare R, Durandy A, Lammas D, Emile JF, Lamhamedi S, Le Deist F, Drysdale P, Jouanguy E, Doffinger R, Bernaudin F, Jeppsson O, Gollob JA, Meinl E, Segal AW, Fischer A, Kumararatne D, Casanova JL (1998) Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science 280:1432Google Scholar

Anne TM, Penix LA, Rincon M, Flavell RA (1997) Differential transcription directed by discrete gamma interferon promoter elements in naive and memory (effector) CD4T cells and CD8T cells. Mol Cell Biol 17:199Google Scholar

Bacon CM, Petricoin EF III, Ortaldo JR, Rees RC, Lamer AC, Johnston JA, O'Shea JJ (1995) Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes. Proc Natl Acad Sci USA 92:7307Google Scholar

Barbulescu K, Becker C, Schlaak JF, Schmitt E, zum Büschenfelde K-HM, Neurath MF (1998) IL-12 and IL-18 differentially regulate the transcriptional activity of the human IFN-γ promoter in primary CD4⁺ T lymphocytes. J Immunol 160:3642Google Scholar

Barton K, Muthusamy N, Fischer C, Ting CN, Walunas TL, Lanier LL, Leiden JM (1998) The Ets-I transcription factor is required for the development of natural killer cells in mice. Immunity 9:555Google Scholar

Bendelac A, Killeen N, Littman DR, Schwartz RH (1994) A subset of CD4+ thymocytes selected by MHC class I molecules. Science 263:1774Google Scholar

Bird JJ, Brown DR, Mullen AC, Moskowitz NH, Mahowald MA, Sider JR, Gajewski TF, Wang C-R, Reiner SL (1998) Helper T cell differentiation is controlled by the cell cycle. Immunity 9:229Google Scholar

Bradding P, Feather IH, Howarth PH, Mueller R, Roberts JA, Britten K, Bews JPA, Hunt TC, Okayama Y, Heusser CH, Bullock GR, Church MK, Holgate ST (1992) Interleukin 4 is localized to and released by human mast cells. J Exp Med 176:1381Google Scholar

Brinkmann V, Geiger T, Alkan S, Heusser CH (1993) Interferon a increases the frequency of interferon γ-producing human CD4⁺ T cells. J Exp Med 178:1655Google Scholar

Cantrell D (1996) T cell antigen receptor signal transduction pathways. Annu Rev Immunol 14:259Google Scholar

Carter LL, Murphy KM (1999) Lineage-specific requirement for signal transducer and activator of transcription (Stat)4 in interferon 7 production from CD4⁺ versus CD8⁺ T cells. J Exp Med 189:1355Google Scholar

Chan SH, Perussia B, Gupta JW, Kobayashi M, Pospisil M, Young HA, Wolf SF, Young D, Clark SC, Trinchieri G (1991) Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers. J Exp Med 173:869Google Scholar

Chen H, Paul WE (1997) Cultured NK1.l⁺ CD4⁺ T cells produce large amounts of IL-4 and IFN-gamma upon activation by anti-CD3 or CD1. J Immunol 159:2240Google Scholar

Cho S, Bacon CM, Sudarshan C, Rees RC, Finbloom D, Pine R, O'Shea JJ (1996) Activation of STAT4 by IL-12 and IFN-α. Evidence for the involvement of ligand-induced tyrosine and serine phosphorylation. J Immunol 157:4781Google Scholar

Chua AO, Chizzonite R, Desai BB, Truitt TP, Nunes P, Minetti LJ, Warrier RR, Presky DH, Levine JF, Gately MK, Goblet U (1994) Expression cloning of a human IL-12 receptor component. A new member of the cytokine receptor superfamily with strong homology to gp130. J Immunol 153:128Google Scholar

Coffman RL, Reiner SL (1999) Instruction, selection, or tampering with the odds? Science 284:1283Google Scholar

Cohen B, Novick D, Barak S, Rubinstein M (1995) Ligand-induced association of the type I interferon receptor components. Mol Cell Biol 15:4208Google Scholar

Colamonici OR, Yan H, Domanski P, Handa R, Smalley D, Mullersman J, Witte M, Krishnan K, Krolewski JJ (1994) Direct binding to and tyrosine phosphorylation of the α subunit of the type I interferon receptor by p135^tyk2 tyrosine kinase. Mol Cell Biol 14:8133Google Scholar

Constant S, Bottomly K (1997) Induction of Th1 and Th2 CD4⁺ T cell responses: the alternative approaches. Annu Rev Immunol 15:297Google Scholar

Constant S, Pfeiffer C, Woodard A, Pasqualini T, Bottomly K (1995) Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells. J Exp Med 182:1591Google Scholar

Crepieux P, Colt J, Stehelin D (1994) The Ets family of proteins: weak modulators of gene expression in quest for transcriptional partners. Crit Rev Oncog 5:615Google Scholar

David M, Chen HE, Goelz S, Larner AC, Neel BG (1995) Differential regulation of the alpha/beta interferon-stimulated Jak/Stat pathway by the SH2 domain-containing tyrosine phosphatase SHPTP1. Mol Cell Biol 15:7050Google Scholar

David M, Zhou G, Pine R, Dixon JE, Larner AC (1996) The SH2 domain-containing tyrosine phosphatase PTP1D is required for interferon α/β-induced gene expression. J Biol Chem 271:15862Google Scholar

De Jong R, Altare R, Haagen IA, Elferink DG, Boer T, Breda Vriesman PJ van, Kabel PJ, Draaisma JM, Dissel JT van, Kroon FP, Casanova JL, Ottenhoff TH (1998) Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. Science 280:1435Google Scholar

Domanski P, Fish EN, Nadeau OW, Witte M, Platanias LC, Yan H, Krolewski JJ, Pitha P, Colamonici OR (1997) A region of the β subunit of the interferon α receptor different from box 1 interacts with Jak1 and is sufficient to activate the Jak-Stat pathway and induce an antiviral state. J Biol Chem 272:26388Google Scholar

Domanski P, Witte M, Kellum M, Rubinstein M, Hackett R, Pitha P, Colamonici OR (1995) Cloning and expression of a long form of the β subunit of the interferon αβ receptor that is required for signaling. J Biol Chem 270:21606Google Scholar

Finkelman FD, Holmes J, Katona IM, Urban JJ, Beckmann MP, Park LS, Schooley KA, Coffman RL, Mosmann TR, Paul WE (1990) Lymphokine control of in vivo immunoglobulin isotype selection. Annu Rev Immunol 8:303Google Scholar

Gately MK, Renzetti LM, Magram J, Stern AS, Adorini L, Gubler U, Presky DH (1998) The interleukin-12/interleukin-l2-receptor system: role in normal and pathologic immune responses. Annu Rev Immunol 16:495Google Scholar

Gauchat JF, Schlagenhauf E, Feng NP, Moser R, Yamage M, Jeannin P, Alouani S, Elson G, Notarangelo LD, Wells T, Eugster HP, Bonnefoy JY (1997) A novel 4-kb interleukin-13 receptor alpha mRNA expressed in human B, T and endothelial cells encoding an alternate type-11 interleukin-4/interleukin-13 receptor. Eur J Immunol 27:971Google Scholar

Gett AV, Hodgkin PD (1998) Cell division regulates the T cell cytokine repertoire, revealing a mechanism underlying immune class regulation. Proc Natl Acad Sci USA 95:9488Google Scholar

Ghayur T, Banerjee S, Hugunin M, Butler D, Herzog L, Carter A, Quintal L, Sekut L, Talanian R, Paskind M, Wong W, Kamen R, Tracey D, Allen H (1997) Caspase-1 processes IFN-7-inducing factor and regulates LPS-induced IFN-γ production. Nature 386:619Google Scholar

Gorham JD, Guler ML, Murphy KM (1997) Genetic control of interleukin 12 responsiveness: implications for disease pathogenesis. J Mol Med 75:502Google Scholar

Gorham JD, Güler ML, Steen RG, Mackey A, Daly MJ, Frederick K, Dietrich WF, Murphy KM (1996) Genetic mapping of a murine locus controlling development of T helper 1/T helper 2 type responses. Proc Natl Acad Sci USA 93:12 467Google Scholar

Graber P, Gretener D, Herren S, Aubry JP, Elson G, Poudrier J, Lecoanet-Henchoz S, Aouani S, Losberger C, Bonnefoy JY, Koseo-Vilbois MH, Gauchat JF (1998) The distribution of IL-13 receptor alphal expression on B cells, T cells and monocytes and its regulation by IL-13 and IL-4. Eur J Immunol 28:4286Google Scholar

Grakoui A, Donermeyer DL, Kanagawa O, Murphy KM, Allen PM (1999) TCR-independent pathways mediate the effects of antigen dose and altered peptide ligands on Th cell polarization. J Immunol 162:1923Google Scholar

Gross A, Ben-Sasson SZ, Paul WE (1993) Anti-IL-4 diminishes in vivo priming for antigen-specific IL-4 production by T cells. J Immunol 150:2112Google Scholar

Gu Y, Kuida K, Tsutsui H, Ku G, Hsiao K, Fleming MA, Hayashi N, Higashino K, Okamura H, Nakanishi K, Kurimoto M, Tanimoto T, Flavell RA, Sato V, Harding MW, Livingston DJ, Su MSS (1997) Activation of interferon-γ inducing factor mediated by interleukin-1β converting enzyme. Science 275:206Google Scholar

Guler ML, Gorham JD, Dietrich WF, Murphy TL, Steen RG, Parvin CA, Fenoglio D, Grupe A, Peltz G, Murphy KM (1999) Tpm1, a locus controlling IL-12 responsiveness, acts by a cell-autonomous mechanism. J Immunol 162:1339Google Scholar

Güler ML, Gorham JD, Hsieh C-S, Mackey A, Steen RG, Dietrich WF, Murphy KM (1996) Genetic susceptibility toLeishmania: IL-12 responsiveness in Th1 cell development. Science 271:984Google Scholar

Güler ML, Jacobson NG, Gubler U, Murphy KM (1997) T cell genetic background determines maintenance of IL-12 signaling. Effects on BALB/c and B10.D2 T helper cell type 1 phenotype development. J Immunol 159:1767Google Scholar

Henkel G, Brown MA (1994) PU.1 and GATA: components of a mast cell-specific interleukin 4 intronic enhancer. Proc Natl Acad Sci USA 91:7737Google Scholar

Henkel G, Weiss DL, McCoy R, Deloughery T, Tara D, Brown MA (1992) A DNase I-hypersensitive site in the second intron of the murine IL-4 gene defines a mast cell-specific enhancer. J Immunol 149:3239Google Scholar

Ho I-C, Hodge MR, Rooney JW, Glimcher LH (1996) The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4. Cell 85:973Google Scholar

Ho I-C, Lo D, Glimcher LH (1998) c-maf promotes T helper cell type 2 (Th2) and attenuates Th1 differentiation by both interleukin 4-dependent and -independent mechanisms. J Exp Med 188:1859Google Scholar

Hodge MR, Chun HJ, Rengarajan J, Alt A, Lieberson R, Glimcher LH (1996) NF-AT-driven interleukin-4 transcription potentiated by NIP45. Science 274:1903Google Scholar

Hodge MR, Ranger AM, Brousse C de la, Hoey T, Grusby MJ, Glimcher LH (1996) Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice. Immunity 4:397Google Scholar

Hodge MR, Rooney JW, Glimcher LH (1995) The proximal promoter of the IL-4 gene is composed of multiple essential regulatory sites that bind at least two distinct factors. J Immunol 154:6397Google Scholar

Horvath CM, Stark GR, Kerr IM, Darnell JE (1996) Interactions between STAT and non-STAT proteins in the interferon-stimulated gene factor 3 transcription complex. Mol Cell Biol 16:6957Google Scholar

Hosken NA, Shibuya K, Heath AW, Murphy KM, O'Garra A (1995) The effect of antigen dose on CD4⁺ T helper cell phenotype development in a T cell receptor-α-transgenic model. J Exp Med 182:1579Google Scholar

Hou J, Schindler U, Henzel WJ, Ho TC, Brasseur M, McKnight SL (1994) An interleukin-4-induced transcription factor: IL-4 Stat. Science 265:1701Google Scholar

Hsieh C-S, Macatonia SE, O'Garra A, Murphy KM (1995) T cell genetic background determines default T helper phenotype development in vitro. J Exp Med 181:713Google Scholar

Hsieh C-S, Macatonia SE, Tripp CS, Wolf SF, O'Garra A, Murphy KM (1993) Development of Th1 CD4⁺ T cells through IL-12 produced byListeria-induced macrophages. Science 260:547Google Scholar

Hubank M, Schatz DG (1994) Identifying differences in mRNA expression by representational difference analysis of cDNA. Nucleic Acids Res 22:5640Google Scholar

Hubank M, Schatz DG (1999) cDNA representational difference analysis: a sensitive and flexible method for identification of differentially expressed genes. Methods Enzymol 303:325Google Scholar

Improta T, Schindler C, Horvath CM, Kerr IM, Stark GR, Darnell JE (1994) Transcription factor ISGF-3 formation requires phosphorylated Stat91 protein, but Statl 13 protein is phosphorylated independently of Stat91 protein. Proc Natl Acad Sci USA 91:4776Google Scholar

Izuhara K, Harada N (1993) Interleukin-4 (IL-4) induces protein tyrosine phosphorylation of the IL-4 receptor and association of phosphatidylinositol 3-kinase to the IL-4 receptor in a mouse T cell line, HT2. J Biol Chem 268:13 097Google Scholar

Jacobson NG, Szabo SJ, Guler ML, Gorham JD, Murphy KM (1996) Regulation of interleukin-12 signalling during T helper phenotype development. 62nd Forum in Immunology 146:446Google Scholar

Jacobson NG, Szabo SJ, Weber-Nordt RM, Zhong Z, Schreiber RD, Darnell JE, Murphy KM (1995) Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4. J Exp Med 181:1755Google Scholar

Kaplan MH, Schindler U, Smiley ST, Grusby MJ (1996) Stat6 is required for mediating responses to IL-4 and for the development of Th2 cells. Immunity 4:313Google Scholar

Kaplan MH, Sun Y-L, Hoey T, Grusby MJ (1996) Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Science 382:174Google Scholar

Keegan AD, Johnston JA, Tortolani PJ, McReynolds LJ, Kinzer C, O'Shea JJ, Paul WE (1995) Similarities and differences in signal transduction by interleukin 4 and interleukin 13: analysis of Janus kinase activation. Proc Natl Acad Sci USA 92:7681Google Scholar

Keegan AD, Nelms K, White M, Wang L-M, Pierce JH, Paul WE (1994) An IL-4 receptor region containing an insulin receptor motif is important for IL-4-mediated IRS-1 phosphorylation and cell growth. Cell 76:811Google Scholar

Kessler DS, Veals SA, Fu X-Y, Levy DE (1990) Interferon-a regulates nuclear translocation and DNA-binding affinity of ISGF3, a multimeric transcriptional activator. Genes Dev 4:1753Google Scholar

Kiani A, Viola JPB, Lichtman AH, Rao A (1997) Down-regulation of IL-4 gene transcription and control of Th2 cell differentiation by a mechanism involving NFAT1. Immunity 7:849Google Scholar

Kobayashi M, Fitz L, Ryan M, Hewick RM, Clarck SC, Chan S, Loudon R, Sherman F, Perussia B, Trinchieri G (1989) Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med 170:827Google Scholar

Kohno K, Kataoka J, Ohtsuki T, Suemoto Y, Okamoto I, Usui M, Ikeda M, Kurimoto M (1997) IFN-gamma-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12. J Immunol 158:1541Google Scholar

Kopf M, Le Gros G, Bachmann M, Lamers MC, Bluethmann H, Kohler G (1993) Disruption of the marine IL-4 gene blocks Th2 cytokine responses. Nature 362:245Google Scholar

Krishnan K, Singh B, Krolewski JJ (1998) Identification of amino acid residues critical for the Src-homology 2 domain-dependent docking of Stat2 to the interferon a receptor. J Biol Chem 273:19 495Google Scholar

Kubo M, Ransom J, Webb D, Hashimoto Y, Tada T, Nakayama T (1997) T-cell subset-specific expression of the IL-4 gene is regulated by a silencer element and STAT6. EMBO J 16:4007Google Scholar

Kühn R, Rajewsky K, Müller W (1991) Generation and analysis of interleukin-4 deficient mice. Science 254:707Google Scholar

Leung S, Qureshi SA, Kerr IM, Darnell JE, Stark GR (1995) Role of STAT2 in the alpha interferon signaling pathway. Mol Cell Biol 15:1312Google Scholar

Li B, Tournier C, Davis RJ, Flavell RA (1999) Regulation of IL-4 expression by the transcription factor JunB during T helper cell differentiation. EMBO J 18:420Google Scholar

Li X, Leung S, Qureshi SA, Darnell JE, Stark GR (1996) Formation of STATI-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferon-α. J Biol Chem 271:5790Google Scholar

Macatonia SE, Hosken NA, Litton M, Vieira P, Hsieh C-S, Culpepper JA, Wysocka M, Trinchieri G, Murphy KM, O'Garra A (1995) Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4⁺ T cells. J Immunol 154:5071Google Scholar

Macatonia SE, Hsieh C-S, Murphy KM, O'Garra A (1993) Dendritic cells and macrophages are required for Th1 development of CD4⁺ T cells from αβ TCR trausgenic mice: IL-12 substitution for macrophages to stimulate IFN-γ production is IFN-γ-dependent. Int Immunol 9:1119Google Scholar

Magram J, Connaughton SE, Warrier RR, Carvajal DM, Wu CY, Ferrante J, Stewart C, Sarmiento U, Faherty DA, Gately MK (1996) IL-12-deficient mice are defective in IFN gamma production and type 1 cytokine responses. Immunity 4:471Google Scholar

Marsh DG, Neely JD, Breazeale DR, Ghosh B, Freidhoff LR, Erlich-Kautzky E, Schou C, Krishnaswamy G, Beaty TH (1994) Linkage analysis of IL4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations. Science 264:1152Google Scholar

Martinez-Moczygemba M, Gutch MJ, French DL, Reich NC (1997) Distinct STAT structure promotes interaction of STAT2 with the p48 subunit of the interferon-α-stimulated transcription factor ISGF3. J Biol Chem 272:20070Google Scholar

Matsumoto S, Tsuji-Takayama K, Aizawa Y, Koide K, Takeuchi M, Ohta T, Kurimoto M (1997) Interleukin-18 activates NF-κB in murine T helper type 1 cells. Biochem Biophys Res Commun 234:454Google Scholar

McKenzie GJ, Emson CL, Bell SE, Anderson S, Fallon P, Zurawski G, Murray R, Grencis R, McKenzie ANJ (1998) Impaired development of Th2 cells in IL-13-deficient mice. Immunity 9:423Google Scholar

Minty A, Chalon P, Derocq J-M, Dumont X, Guillemot J-C, Kaghad M, Labit C, Leplatois P, Liauzun P, Miloux B, Minty C, Casellas P, Loison G, Lupker J, Shire D, Ferrara P, Caput D (1993) Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses. Nature 362:248Google Scholar

Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu ZJ, Oishi I, Silvennoinen O, Witthuhn BA, Ihle JN, Taniguchi T (1994) Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits. Science 266:1045Google Scholar

Mosley B, Beckmann MP, March CJ, Idzerda RL, Gimpel SD, VandenBos T, Friend D, Alpert A, Anderson D, Jackson J, Wignall JM, Smith C, Gallis B, Sims JE, Urdal D, Widmer MB, Cosman D, Park LS (1989) The murine interleukin-4 receptor: molecular cloning and characterization of secreted and membrane bound forms. Cell 59:335Google Scholar

Murphy KM, Murphy TL, Szabo SJ, et al (1997) Regulation of IL-12 receptor expression in early Thelper responses implies two phases of Th1 differentiation: capacitance and development. In: Adorini L (ed) Chemical immunology. Karger, Basel, pp 54–69Google Scholar

Naeger LK, McKinney J, Salvekar A, Hoey T (1999) Identification of a STAT4 binding site in the interleukin-12 receptor required for signaling. J Biol Chem 274:1875Google Scholar

Novick D, Cohen B, Rubinstein M (1994) The human interferon a /(3 receptor: characterization and molecular cloning. Cell 77:391Google Scholar

Okamura H, Tsutsui H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K, Akita K, Namba M, Tanabe F, Konishi K, Fukuda S, Kurimoto M (1995) Cloning of a new cytokine that induces IFN-γ production by T cells. Nature 378:88Google Scholar

Oukka M, Ho I-C, Brousse C de la, Hoey T, Grusby MJ, Glimcher LH (1998) The transcription factor NFAT4 is involved in the generation and survival of T cells. Immunity 9:295Google Scholar

Ouyang W, Jacobson NG, Bhattacharya D, Gorham JD, Fenoglio D, Sha WC, Murphy TL, Murphy KM (1999) The Ets transcription factor ERM is Th1-specific and induced by IL-12 through a Stat4-dependent pathway. Proc Natl Acad Sci USA 96:3888Google Scholar

Ouyang W, Ranganath SH, Weindel K, Bhattacharya D, Murphy TL, Sha WC, Murphy KM (1998) Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism. Immunity 9:745Google Scholar

Pandolfi PP, Roth ME, Karis A, Leonard MW, Dzierzak E, Grosveld FG, Engel JD, Lindenbaum MH (1995) Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis. Nat Genet 11:40Google Scholar

Parronchi P, De Carli M, Manetti R, Simonelli C, Sampognaro S, Piccinni M-P, Macchia D, Maggi E, Del Prete G, Romangnani S (1992) IL-4 and IFN (α and γ) exert opposite regulatory effects on the development of cytolytic potential by Th1 or Th2 human T cell clones. J Immunol 149:2977Google Scholar

Penix LA, Sweetser MT, Weaver WM, Hoeffler JP, Kerppola TK, Wilson CB (1996) The proximal regulatory element of the interferon-gamma promoter mediates selective expression in T cells. J Biol Chem 271:31964Google Scholar

Penix LA, Weaver WM, Pang Y, Young HA, Wilson CB (1993) Two essential regulatory elements in the human interferon gamma promoter confer activation specific expression in T cells. J Exp Med 178:1483Google Scholar

Pfeffer LM, Mullersman JE, Pfeffer SR, Murti A, Shi W, Yang CH (1997) STAT3 as an adapter to couple phosphatidylinositol 3-kinase to the IFNAR1 chain of the type I interferon receptor. Science 276:1418Google Scholar

Presky DH, Yang H, Minetti LJ, Chua AO, Nabavi N, Wu C-Y, Gately MK, Gubler U (1996) A functional interleukin 12 receptor complex is composed of two β-type cytokine receptor subunits. Proc Natl Acad Sci USA 93:14 002Google Scholar

Quelle FW, Shimoda K, Thierfelder WE, Fischer C, Kim A, Ruben SM, Cleveland JL, Pierce JH, Keegan AD, Nelms K, Paul WE, Ihle JN (1995) Cloning of murine Stat6 and human Stat6, Stat proteins that are tyrosine phosphorylated in responses to IL-4 and IL-3 but are not required for mitogenesis. Mol Cell Biol 15:3336Google Scholar

Qureshi SA, Leung S, Kerr IM, Stark GR, Darnell JE (1996) Function of Stat2 protein in transcriptional activation by alpha interferon. Mol Cell Biol 16:288Google Scholar

Qureshi SA, Salditt-Teorgieff M, Darnell JE (1995) Tyrosine-phosphorylated Statl and Stat2 plus a 48-kDa protein all contact DNA in forming interferon-stimulated-gene factor 3. Proc Natl Acad Sci USA 92: 3829Google Scholar

Ranganath SH, Ouyang W, Bhattacharya D, Sha WC, Grupe A, Peltz G, Murphy KM (1998) GATA3-dependent enhancer activity in IL-4 gene regulation. J Immunol 161:3822Google Scholar

Ranger AM, Hodge MR, Gravellese EM, Oukka M, Davidson L, Alt FW, Brousse C de la, Hoey T, Grusby MJ, Glimcher LH (1998) Delayed lymphoid repopulation with defects in IL-4-driven responses produced by inactivation of NF-ATc. Immunity 8:125Google Scholar

Ranger AM, Oukka M, Rengarajan J, Glimcher LH (1998) Inhibitory function of two NFAT family members in lymphoid homeostasis and Th2 development. Immunity 9:627Google Scholar

Rao A, Luo C, Hogan PG (1997) Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol 15:707Google Scholar

Reiner SL, Locksley RM (1995) The regulation of immunity toLeishmania major. Anon Rev Immunol 13:151Google Scholar

Robinson D, Shibuya K, Mui A, Zonin F, Murphy E, Sana T, Hartley SB, Menon S, Kastelein R, Bazan F, O'Garra A (1997) IGIF does not drive Th1 development but synergizes with IL-12 for interferon-γ production and activates IRAK and NFκB. Immunity 7:571Google Scholar

Rogge L, Barberis-Maino L, Biffi M, Passini N, Presky DH, Gubler U, Sinigaglia F (1997) Selective expression of an interleukin-12 receptor component by human T helper 1 cells. J Exp Med 185:825Google Scholar

Rogge L, D'Ambrosio D, Biffi M, Penna G, Minetti IJ, Presky DH, Adorini L, Sinigaglia F (1998) The role of Stat4 in species-specific regulation of Th cell development by type I IFNs. J Immunol 161:6567Google Scholar

Rooney JW, Hoey T, Glimcher LH (1995) Coordinate and cooperative roles for NF-AT and AP-1 in the regulation of the murine IL-4 gene. Immunity 2:473Google Scholar

Russell SM, Keegan AD, Harada N, Nakamura Y, Noguchi M, Leland P, Friedmann MC, Miyajima A, Puri RK, Paul WE, Leonard WJ (1993) Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor. Science 262:1880Google Scholar

Ryan JJ, McReynolds LJ, Keegan A, Wang L-H, Garfein E, Rothman P, Nelms K, Paul WE (1996) Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor. Immunity 4:132Google Scholar

Sad S, Marcotte R, Mosmann TR (1995) Cytokine-induced differentiation of precursor mouse Cd8⁺ T cells into cytotoxic CD8⁺ T cells secreting Th1 or Th2 cytokines. Immunity 2:271Google Scholar

Schmitz J, Thiel A, Kühn R, Rajewsky K, Müller W, Assenmacher M, Radbruch A (1994) Induction of interleukin 4 (IL-4) expression in T helper (Th) cells is not dependent on IL-4 from non-Th cells. J Exp Med 179:1349Google Scholar

Seder RA, Paul WE, Ben-Sasson SZ, LeGros GS, Kagey-Sobotka A, Finkelman FD, Pierce JH, Plant M (1991) Production of interleukin-4 and other cytokines following stimulation of mast cell lines and in vivo mast cells/basophils. Int Arch Allergy Appl Immunol 94:137Google Scholar

Seder RA, Paul WE, Davis MM, Fazekas de St Groth B (1992) The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4⁺ T cells from T cell receptor transgenic mice. J Exp Med 176:1091Google Scholar

Shimoda K, Deursen J van, Sangster MY, Sarawar SR, Carson RT, Tripp RA, Chu C, Quelle FW, Nosaka T, Vignali DAA, Doherty PC, Grosveld G, Paul WE, Ihle JN (1996) Lack of IL-4-induced Th2 response and IgE class switching in mice with disruptedStat6 gene. Nature 380:630Google Scholar

Shuai K, Horvath CM, Tsai Huang LH, Qureshi SA, Cowburn D, Darnell JE (1994) Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions. Cell 76:821Google Scholar

Smiley ST, Kaplan MH, Grusby MJ (1997) Immunoglobulin E production in the absence of interleukin-4-secreting CD1-dependent cells. Science 275:977Google Scholar

Snapper C, Paul WE (1987) Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science 236:944Google Scholar

Stark GR, Kerr IM, Williams BR, Silverman RH, Schreiber RD (1998) How cells respond to interferons. Annu Rev Biochem 67:227Google Scholar

Swain SL, McKenzie DT, Weinberg AD, Hancock W (1988) Characterization of T helper 1 and 2 subsets in normal mice. Helper T cells responsible for IL-4 and IL-5 production are present as precursors that require priming before they develop into lymphokine-secreting cells. J Immunol 141:3445Google Scholar

Swain SL, Weinberg AD, English M, Huston G (1990) IL-4 directs the development of Th2-like helper effectors. J Immunol 145:3796Google Scholar

Szabo SJ, Dighe AS, Gubler U, Murphy KM (1997) Regulation of the interleukin (IL)-12R β2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J Exp Med 185:817Google Scholar

Szabo SJ, Gold JS, Murphy TL, Murphy KM (1993) Identification of cis-acting regulatory elements controlling interleukin-4 gene expression in T cells: roles for NF-Y and NF-ATc. Mol Cell Biol 13:4793Google Scholar

Szabo SL, Jacobson NG, Dighe AS, Gubler U, Murphy KM (1995) Developmental commitment to the Th2 lineage by extinction of IL-12 signaling. Immunity 2:665Google Scholar

Takeda K, Tanaka T, Shi W, Matsumoto M, Minami M, Kashiwamura S, Nakanishi K, Yoshida N, Kishimoto T, Akira S (1996) Essential role of Stat6 in IL-4 signalling. Nature 380:627Google Scholar

Takeda K, Tsutsui H, Yoshimoto T, Adachi O, Yoshida N, Kishimoto T, Okamura H, Nakanishi K, Akira S (1998) Defective NK cell activity and Th1 response in IL-18-deficient mice. Immunity 8:383Google Scholar

Ting C-N, Olson MC, Barton KP, Leiden JM (1996) Transcription factor GATA-3 is required for development of the T-cell lineage. Nature 384:474Google Scholar

Todd MD, Grusby MJ, Lederer J, Lacy E, Lichtman AH, Glimcher LH (1993) Transcription of the interleukin 4 gene is regulated by multiple promoter elements. J Exp Med 177:1663Google Scholar

Tomura M, Maruo S, Mu J, Zhou X-Y, Alm H-J, Hamaoka T, Okamura H, Nakanishi K, Clark S, Kurimoto M, Fujiwara H (1998) Differential capacities of CD4⁺, CD8⁺, and CD4-CD8⁻ T cell subsets to express IL-18 receptor and produce IFN-γ in response to IL-18. J Immunol 160:3759Google Scholar

Uddin S, Chamdin A, Platanias LC (1995) Interaction of the transcriptional activator Stat-2 with the type I interferon receptor. J Biol Chem 270:24 627Google Scholar

Urban JE, Noben-Trauth N, Donaldson DD, Madden KB, Morris SC, Collins M, Finkelman FD (1998) IL-13, IL-4Rα, and Stat6 are required for the expulsion of the gastrointestinal nematode parasiteNippostrongylus brasiliensis. Immunity 8:255Google Scholar

Wang HY, Paul WE, Keegan AD (1996) IL-4 function can be transferred to the IL-2 receptor by tyrosine containing sequences found in the IL-4 receptor α chain. Immunity 4:113Google Scholar

Wang L-M, Keegan AD, Paul WE, Heidaran MA, Gutkind JS, Pierce JH (1992) IL-4 activates a distinct signal transduction cascade from IL-3 in factor-dependent myeloid cells. EMBO J 11:4899Google Scholar

Wang LM, Keegan AD, Li W, Lienhard GE, Pacini S, Gutkind JS, Myers MG Jr, Sun XJ, White ME, Aaronson SA, Paul WE, Pierce JH (1993) Common elements in interleukin 4 and insulin signaling pathways in factor-dependent hematopoietic cells. Proc Natl Acad Sci USA 90:4032Google Scholar

Wang Z, Reiner SL, Zheng S, Dalton DK, Locksley RM (1994) CD4⁺ effector cells default to the Th2 pathway in interferon g-deficient mice infected with Leishmania major. J Exp Med 179:1367Google Scholar

Wenner CA, Güler ML, Macatonia SE, O'Garra A, Murphy KM (1996) Roles of IFN-γ and IFN-α in IL-12-induced T helper cell-1 development. J Immunol 156:1442Google Scholar

Wenner CA, Szabo SJ, Murphy KM (1997) Identification of IL-4 promoter elements conferring Th2-restricted expression during T helper cell subset development. J Immunol 158:765Google Scholar

Wu C, Ferrante J, Gately MK, Magram J (1997) Characterization of IL-12 receptor betal chain (IL-12Rβ1)-deficient mice: IL-12Rβ1 is an essential component of the functional mouse IL-12 receptor. J Immunol 159:1658Google Scholar

Xanthoudakis S, Viola JPB, Shaw KTY, Luo C, Wallace JD, Bozza PT, Curran T, Rao A (1996) An enhanced immune response in mice lacking the transcription factor NFAT1. Science 272:892Google Scholar

Xu D, Chan WL, Leung BP, Hunter D, Schulz K, Carter RW, McInnes IB, Robinson JH, Liew FY (1998) Selective expression and functions of interleukin 18 receptor on T helper (Th) type 1 but not Th2 cells. J Exp Med 188:1485Google Scholar

Yan H, Krishnan K, Greenlund AC, Gupta S, Lim JTE, Schreiber RD, Schindler CW, Krolewski JJ (1996) Phosphorylated interferon-α receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein. EMBO J 15:1064Google Scholar

Yan H, Krishnan K, Lim JTE, Contillo LG, Krolewski JJ (1996) Molecular characterization of an alpha interferon receptor 1 subunit (IFNaR1) domain required for TYK2 binding and signal transduction. Mol Cell Biol 16:2074Google Scholar

Yang C-H, Shi W, Basu L, Murti A, Constantinescu SN, Blatt L, Croze E, Mullersman JE, Pfeffer LM (1996) Direct association of STAT3 with the IFNAR-1 chain of the human type I interferon receptor. J Biol Chem 271:8057Google Scholar

Yang J, Murphy TL, Ouyang W, Murphy KM (1999) Induction of interferon-γ production in Thl CD4⁺ T cells: evidence for two distinct pathways for promoter activation. Eur J Immunol 29:548Google Scholar

Yin T, Tsang ML, Yang YC (1994) JAK1 kinase forms complexes with interleukin-4 receptor and 4PS/insulin receptor substrate-1-like protein and is activated by interleukin-4 and interleukin-9 in T lymphocytes. J Biol Chem 269:26614Google Scholar

Yoshida H, Nishina H, Takimoto H, Marengere LEM, Wakeham AC, Bouchard D, Kong Y-Y, Ohteki T, Shahinian A, Bachmann M, Ohashi PS, Penninger JM, Crabtree GR, Mak TW (1998) The transcription factor NF-ATc1 regulates lymphocyte proliferation and Th2 cytokine production. Immunity 8:115Google Scholar

Yoshimoto T, Bendelac A, Watson C, Hu-Li J, Paul WE (1995) Role of NK1.1⁺ T cells in a Th2 response and in immunoglobulin E production. Science 270:1845Google Scholar

Yoshimoto T, Takeda K, Tanaka T, Ohkusu K, Kashiwamura S, Okamura H, Akira S, Nakanishi K (1998) IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-γ production. J Immunol 161:3400Google Scholar

Zhang D-H, Cohn L, Ray P, Bottomly K, Ray A (1997) Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. J Biol Chem 272:21597Google Scholar

Zheng W-P, Flavell RA (1997) The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 89:587Google Scholar

Zou J, Presky DH, Wu C-Y, Gubler U (1997) Differential associations between the cytoplasmic regions of the interleukin-12 receptor subunits β1 and β2 and JAK kinases. J Biol Chem 272:6073Google Scholar