Abstract
The functional specialization of T effector cells according to cytokine secretion patterns has been recognized as an important parameter shaping local immune responses. Here we discuss evidence that T cell subsets might also develop distinctive properties related to homing and trafficking into inflamed sites. First, ligands for the inflammation-induced endothelial selectins were found to be induced by IL-12, and hence selectively expressed on Th1 cells generated in vitro. However, their expression on effector cells occuring in vivo is less well correlated with the Th subset. Second, a variety of receptors for and responses towards chemokines have been found to be differentially associated with Th subsets. Notably CCR5 and, to a lesser degree CXCR3 were preferentially found on Th1 cells, CCR4, CCR8 and, more controversial, CCR3 and CXCR4 on Th2 cells. Although many points, such as stability of the phenotype versus dependency on inducing cytokines and activation stages remain to be clarified, it appears that this field provides new insights into the regulation of locally balanced activities of Th subsets and might constitute a promising field for the development of new immunosuppressive drugs.
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References
Weiner HL (1997) Oral tolerance: immune mechanisms and treatment of autoimmune diseases. Immunol Today 18:335
Brandtzaeg P, Farstad IN, Haraldsen G (1999) Regional specialization in the mucosal immune system: primed cells do not always home along the same track. Immunol Today 20:267
Huang L, Soldevilla G, Leeker M, Flavell R, Crispe IN (1994) The liver eliminates T cells undergoing antigen-triggered apoptosis in vivo. Immunity 1:741
Mehal WZ, Juedes AE, Crispe IN (1999) Selective retention of activated CD8+ T cells by the normal liver. J Immunol 163:3202
Hamann A, Rebstock S (1993) Migration of activated lymphocytes. Curr Top Microbiol Immunol 184:109
Hamann A (1997) Specific trafficking: which cells, which function? In: Hamann A (ed) Adhesion molecules and chemokines in lymphocyte trafficking. Cell adhesion and communication. Harwood. Chur, p 1
Gowans JL, Knight EJ (1964) The route of recirculation of lymphocytes in the rat. Proc Roy Soc Lond B 159:257
Guy-Grand D, Griscelli C, Vassalli P (1974) The gut associated lymphoid system: nature and properties of the large dividing cells. Eur J Immunol 4:435
Quiding Jabrink M, Nordstrom I, Granstrom G, Kilander A, Jertborn M, Butcher EC, Lazarovits AI, Holmgren J, Czerkinsky C (1997) Differential expression of tissue-specific adhesion molecules on human circulating antibody-forming cells after systemic, enteric, and nasal immunizations. A molecular basis for the compartmentalization of effector B cell responses. J Clin Invest 99:1281
Kantele A, Zivny J, Hakkinen M, Elson CO, Mestecky J (1999) Differential homing commitments of antigen-specific T cells after oral or parenteral immunization in humans. J Immunol 162:5173
Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76:301
Butcher EC, Picker LJ (1996) Lymphocyte homing and homeostasis. Science 272:60
Salmi M, Jalkanen S (1997) How do lymphocytes know where to go: current concepts and enigmas of lymphocyte homing. Adv Immunol 64:139
Hamann A (ed) (1997) Adhesion molecules and chemokines in lymphocyte trafficking. Harwood, Chur
Forster R, Mattis AE, Kremmer E, Wolf E, Brem G, Lipp M (1996) A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen. Cell 87:1037
Homeister JW, Zhang M, Frenette PS, Hynes RO, Wagner DD, Lowe JB, Marks RM (1998) Overlapping functions of E- and P-selectin in neutrophil recruitment during acute inflammation. Blood 92:2345
Austrup F, Vestweber D, Borges E, Löhning M, Bräuer R, Herz U, Renz H, Hallmann R, Scheffold A, Radbruch A, Hamann A (1997) P- and E-selectin mediate recruitment of T helper 1 but not T helper 2 cells into inflamed tissues. Nature 385:81
Tietz W, Allemand Y, Borges E, Laer Dv, Hallmann R, Vestweber D, Hamann A (1998) CD4+ T-cells only migrate into inflamed skin if they express ligands for E- and P-selectin. J Immunol 161:963
Hahne M, Jager U, Isenmann S, Hallmann R, Vestweber D (1993) Five tumor necrosis factor-inducible cell adhesion mechanisms on the surface of mouse endothelioma cells mediate the binding of leukocytes. J Cell Biol 121:655
Yao L, Pan J, Setiadi H, Patel KD, McEver RP (1996) Interleukin 4 or oncostatin M induces a prolonged increase in P-selectin mRNA and protein in human endothelial cells. J Exp Med 184:81
Montgomery KF, Osborn L, Hession C, et al (1991) Activation of endothelial-leukocyte adhesion molecule 1 (ELAM-1) gene transcription. Proc Natl Acad Sci USA 88:6523
Knibbs RN, Craig RA, Maly P, Smith PL, Wolber FM, Faulkner NE, Lowe JB, Stoolman LM (1998) Alpha(1,3)-fucosyltransferase VII-dependent synthesis of P- and E-selectin ligands on cultured T lymphoblasts. J Immunol 161:6305
Xie H, Lim YC, Luscinskas FW, Lichtman AH (1999) Acquisition of selectin binding and peripheral homing properties by CD4(+) and CD8(+) T cells. J Exp Med 189:1765
Berg EL, Yoshino T, Rott LS, Robinson MK, Warnock RA, Kishimoto TK, Picker LJ, Butcher EC (1991) The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule 1. J Exp Med 174:1461
Thoma S, Bonhagen K, Vestweber D, Hamann A, Reimann J (1998) Expression of selectin-binding epitopes and cytokines by CD4+ T cells repopulating scid mice with colitis. Eur J Immunol 28:1785
Hamann A, Jablonski-Westrich D, Duijvestijn A, Butcher EC, Baisch H, Harder R, Thiele H-G (1988) Evidence for an accessory role of LFA-1 in lymphocyte-high endothelium interaction during homing. J Immunol 140:693
Berlin-Rufenach C, Otto F, Mathies M, Westermann J, Owen MJ, Hamann A, Hogg N (1999) ymphocyte migration in LFA-1 deficient mice. J Exp Med 189:1467
Nakache M, Lakey-Berg E, Streeter PR, Butcher EC (1989) The mucosal vascular addressin is a tissue-specific endothelial adhesion molecule for circulating lymph nodes. Nature 337:179
Williams MB, Butcher EC (1997) Homing of naive and memory T lymphocyte subsets to Peyer's patches, lymph nodes, and spleen. J Immunol 159:1746
Meeusen ENT, Premier RR, Brandon MR (1996) Tissue-specific migration of lymphocytes: a key role for Th1 and Th2 cells? Immunol Today 17:421
Adema GJ, Hartgers F, Verstraten R, Vries E de, Marland G, Menon S, Foster J, Xu Y, Nooyen P, McClanahan T, Bacon KB, Figdor CG (1997) A dendritic cell-derived C-C chemokine that preferentially attracts naive T cells. Nature 387:713
Willimann K, Legler DF, Loetscher M, Roos RS, Delgado MB, Clark-Lewis I, Baggiolini M, Moser B (1998) The chemokine SLC is expressed in T cell areas of lymph nodes and mucosal lymphoid tissues and attracts activated T cells via CCR7. Eur J Immunol 28:2025
Gunn MD, Tangemann K, Tam C, Cyster JG, Rosen SD, Williams LT (1998) A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes. Proc Natl Acad Sci USA 95:258
Ngo VN, Tang HL, Cyster JG (1998) Epstein-Barr virus-induced molecule 1 ligand chemokine is expressed by dendritic cells in lymphoid tissues and strongly attracts naive T cells and activated B cells. J Exp Med 188:181
Legler DF, Loetscher M, Roos RS, Clark-Lewis I, Baggiolini M, Moser B (1998) B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5. J Exp Med 187:655
Gunn MD, Ngo VN, Ansel KM, Ekland EH, Cyster JG, Williams LT (1998) A B-cell-homing chemokine made in lymphoid follicles activates Burkitt's lymphoma receptor-1. Nature 391:799
Nagasawa T, Kikutani H, Kishimoto T (1994) Molecular cloning and structure of a pre-B-cell growthstimulating factor. Proc Natl Acad Sci USA 91:2305
Saeki H, Moore AM, Brown MJ, Hwang ST (1999) Cutting edge: secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes. J Immunol 162:2472
Campbell JJ, Bowman EP, Murphy K, Youngman KR, Siam MA, Thompson DA, Wu L, Zlotnik A, Butcher EC (1998) 6-C-kine (SLC), a lymphocyte adhesion-triggering chemokine expressed by high endothelium, is an agonist for the MIP-3beta receptor CCR7. J Cell Biol 141:1053
Yoshida R, Nagira M, Imai T, Baba M, Takagi S, Tabira Y, Akagi J, Nomiyama H, Yoshie O (1998) EBI1-ligand chemokine (ELC) attracts a broad spectrum of lymphocytes: activated T cells strongly upregulate CCR7 and efficiently migrate toward ELC. Int Immunol 10:901
Nagira M, Imai T, Yoshida R, Takagi S, Iwasaki M, Baba M, Tabira Y, Akagi J, Nomiyama H, Yoshie O (1998) A lymphocyte-specific CC chemokine, secondary lymphoid tissue chemokine (SLC), is a highly efficient chemoattractant for B cells and activated T cells. Eur J Immunol 28:1516
Gunn MD, Kyuwa S, Tam C, Kakiuchi T, Matsuzawa A, Williams LT, Nakano H (1999) Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization. J Exp Med 189:451
Chan VW, Kothakota S, Rohan MC, Panganiban-Lustan L, Gardner JP, Wachowicz MS, Winter JA, Williams LT (1999) Secondary lymphoid-tissue chemokine (SLC) is chemotactic for mature dendritic cells. Blood 93:3610
Ngo VN, Korner H, Gunn MD, Schmidt KN, Riminton DS, Cooper MD, Browning JL, Sedgwick JD, Cyster JG (1999) Lymphotoxin alphalbeta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen. J Exp Med 189:403
Guinamard R, Signoret N, Masamichi I, Marsh M, Kurosaki T, Ravetch JV (1999) B cell antigen receptor engagement inhibits stromal cell-derived factor (SDF)-lalpha chemotaxis and promotes protein kinase C (PKC)-induced internalization of CXCR4. J Exp Med 189:1461
D'Apuzzo M, Rolink A, Loetscher M, Hoxie JA, Clark-Lewis I, Melchers F, Baggiolini M, Moser B (1997) The chemokine SDF-1, stromal cell-derived factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4. Eur J Immunol 27:1788
Bleul CC, Fuhlbrigge RC, Casasnovas JM, Aiuti A, Springer TA (1996) A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med 184:1101
Bleul CC, Wu L, Hoxie JA, Springer TA, Mackay CR (1997) The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. Proc Natl Acad Sci USA 94:1925
Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T (1996) Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 382:635.
Ma Q, Jones D, Borghesani PR, Segal RA, Nagasawa T, Kishimoto T, Bronson RT, Springer TA (1998) Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci USA 95:9448
Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T, Nagler A, Ben-Hur H, Many A, Shultz L, Lider O, Alon R, Zipori D, Lapidot T (1999) Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 283:845
Kopydlowski KM, Salkowski CA, Cody MJ, van Rooijen N, Major J, Hamilton TA, Vogel SN (1999) Regulation of macrophage chemokine expression by lipopolysaccharide in vitro and in vivo. J Immunol 163:1537
Sherry B, Espinoza M, Manogue KR, Cerami A (1998) Induction of the chemokine beta peptides, MIP-1 alpha and MIP-1 beta, by lipopolysaccharide is differentially regulated by immunomodulatory cytokines gamma-IFN, IL-10, IL-4, and TGF-beta. Mol Med 4:648
McManus CM, Brosnan CF, Berman JW (1998) Cytokine induction of MIP-1 alpha and MIP-1 beta in human fetal microglia. J Immunol 160:1449
Guo H, Jin YX, Ishikawa M, Huang YM, Meide PH van der, Link H, Xiao BG (1998) Regulation of beta-chemokine mRNA expression in adult rat astrocytes by lipopolysaccharide, proinflammatory and immunoregulatory cytokines. Scand J Immunol 48:502
Peterson PK, Hu S, Salak-Johnson J, Molitor TW, Chao CC (1997) Differential production of and migratory response to beta chemokines by human microglia and astrocytes. J Infect Dis 175:478
Gasperini S, Marchi M, Calzetti F, Laudanna C, Vicentini L, Olsen H, Murphy M, Liao F, Farber J, Cassatella MA (1999) Gene expression and production of the monokine induced by IFN-γ (MIG), IFN-inducible T cell alpha chemoattractant (1-TAC), and IFN-gamma-inducible protein-10 (IP-10) chemokines by human neutrophils. J Immunol 162:4928
Sauty A, Dziejman M, Taha RA, Iarossi AS, Neote K, Garcia-Zepeda EA, Hamid Q, Luster AD (1999) The T cell-specific CXC chemokines IP-10, Mig, and I-TAC are expressed by activated human bronchial epithelial cells. J Immunol 162:3549
Mochizuki M, Bartels J, Mallet AI, Christophers E, Schroder JM (1998) IL-4 induces eotaxin: a possible mechanism of selective eosinophil recruitment in helminth infection and atopy. J Immunol 160:60
Li L, Xia Y, Nguyen A, Lai YH, Feng L, Mosmann TR, Lo D (1999) Effects of Th2 cytokines on chemokine expression in the lung: IL-13 potently induces eotaxin expression by airway epithelial cells. J Immunol 162:2477
Andrew DP, Chang MS, McNinch J, Wathen ST, Rihanek M, Tseng J, Spellberg JP, Elias CG (1998) STCP-1 (MDC) CC chemokine acts specifically on chronically activated Th2 lymphocytes and is produced by monocytes on stimulation with Th2 cytokines IL-4 and IL-13. J Immunol 161:5027
Bonecchi R, Sozzani S, Stine JT, Luini W, D'Amico G, Allavena P, Chantry D, Mantovani A (1998) Divergent effects of interleukin-4 and interferon-gamma on macrophage- derived chemokine production: an amplification circuit of polarized T helper 2 responses. Blood 92:2668
Ganzalo JA, Jia GQ, Aguirre V, Friend D, Coyle AJ, Jenkins NA, Lin GS, Katz H, Lichtman A, Copeland N, Kopf M, Gutierrez-Ramos JC (1996) Mouse eotaxin expression parallels eosinophil accumulation during lung allergic inflammation but it is not restricted to a Th2-type response. Immunity 4:1
Gonzalo JA, Lloyd CM, Kremer L, Finger E, Martinez AC, Siegelman MH, Cybulsky M, Gutierrez-Ramos JC (1996) Eosinophil recruitment to the lung in a murine model of allergic inflammation. The role of T cells, chemokines, and adhesion receptors. J Clin Invest 98:2332
Diab A, Abdalla H, Li HL, Shi FD, Zhu J, Hojberg B, Lindquist L, Wretlind B, Bakhiet M, Link H (1999) Neutralization of macrophage inflammatory protein 2 (MIP-2) and MIP-1 alpha attenuates neutrophil recruitment in the central nervous system during experimental bacterial meningitis. Infect Immun 67:2590
DiPietro LA, Burdick M, Low QE, Kunkel SL, Strieter RM (1998) MIP-1alpha as a critical macrophage chemoattractant in murine wound repair. J Clin Invest 101:1693
Didier PJ, Paradis TJ, Gladue RP (1999) The CC chemokine MIP-lalpha induces a selective monocyte infiltration following intradermal injection into nonhuman primates. Inflammation 23:75
Cross AK, Richardson V, Ali SA, Palmer I, Taub DD, Rees RC (1997) Migration responses of human monocytic cell lines to alpha- and beta-chemokines. Cytokine 9:521
Taub DD, Longo DL, Murphy WJ (1996) Human interferon-inducible protein-10 induces mononuclear cell infiltration in mice and promotes the migration of human T lymphocytes into the peripheral tissues and human peripheral blood lymphocytes-SCID mice. Blood 87:1423
Taub DD, Lloyd AR, Conlon K, Wang JM, Ortaldo JR, Harada A, Matsushima K, Kelvin DJ, Oppenheim JJ (1993) Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells. J Exp Med 177:1809
Deng W, Ohmori Y, Hamilton TA (1994) Mechanisms of IL-4-mediated suppression of IP-10 gene expression in murine macrophages. J Immunol 153:2130
Marfaing-Koka A, Devergne O, Gorgone G, Portier A, Schall TJ, Galanaud P, Emilie D (1995) Regulation of the production of the RANTES chemokine by endothelial cells. Synergistic induction by IFN-γ plus TNF-alpha and inhibition by IL-4 and IL-13. J Immunol 154:1870
Ohmori Y, Hamilton TA (1998) STAT6 is required for the anti-inflammatory activity of interleukin-4 in mouse peritoneal macrophages. J Biol Chem 273:29202
Miyamasu M, Yamaguchi M, Nakajima T, Misaki Y, Morita Y, Matsushima K, Yamamoto K, Hirai K (1999) Th1-derived cytokine IFN-gamma is a potent inhibitor of eotaxin synthesis in vitro. Int Immunol 11:1001
Wagers AJ, Waters CM, Stoolman LM, Kansas GS (1998) Interleukin 12 and interleukin 4 control T cell adhesion to endothelial selectins through opposite effects on alpha l, 3-fucosyltransferase VII gene expression. J Exp Med 188:2225
Lim YC, Henault L, Wagers AJ, Kansas GS, Luscinskas FW, Lichtman AH (1999) Expression of functional selectin ligands on Th cells is differentially regulated by IL-12 and IL-4. J Immunol 162:3193
Borges E, Tietz W, Steegmaier M, Moll T, Hallmann R, Hamann A, Vestweber D (1997) P-Selectin glycoprotein ligand-1 (PSGL-1) on T helper 1 but not on T helper 2 cells binds to P-selectin and supports migration into inflamed skin. J Exp Med 185:573
Leung DY, Gately M, Trumble A, Ferguson Darnell B, Schlievert PM, Picker LJ (1995) Bacterial superantigens induce T cell expression of the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen, via stimulation of interleukin 12 production. J Exp Med 181:747
Yago T, Tsukuda M, Fukushima H, Yamaoka H, Kurata Miura K, Nishi T, Minami M (1998) IL-12 promotes the adhesion of NK cells to endothelial selectins under flow conditions. J Immunol 161:1140
Murphy KM (1998) T lymphocyte differentiation in the periphery. Curr Opin Immunol 10:226
Teraki Y, Picker LJ (1997) Independent regulation of cutaneous lymphocyte-associated antigen expression and cytokine synthesis phenotype during human CD4+ memory T cell differentiation. J Immunol 159:6018
Cerwenka A, Morgan TM, Harmsen AG, Dutton RW (1999) Migration kinetics and final destination of type 1 and type 2 CD8 effector cells predict protection against pulmonary virus infection. J Exp Med 189:423
Sallusto F, Mackay CR, Lanzavecchia A (1997) Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Science 277:2005
Gerber BO, Zanni MP, Uguccioni M, Loetscher M, Mackay CR, Pichler WJ, Yawalkar N, Baggiolini M, Moser B (1997) Functional expression of the ectaxin receptor CCR3 in T lymphocytes co- localizing with eosinophils. Curr Biol 7:836
Bonecchi R, Bianchi G, Bordignon PP, D'Ambrosio D, Lang R, Borsatti A, Sozzani S, Allavena P, Gray PA, Mantovani A, Sinigaglia F (1998) Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med 187:129
Sallusto F, Lenig D, Mackay CR, Lanzavecchia A (1998) Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J. Exp. Med. 187:875
Annunziato F, Cosmi L, Galli G, Beltrame C, Romagnani P, Manetti R, Romagnani S, Maggi E (1999) Assessment of chemokine receptor expression by human Th1 and Th2 cells in vitro and in vivo. J Leukoc Biol 65:691
Grimaldi JC, Yu NX, Grunig G, Seymour BW, Cottrez F, Robinson DS, Hosken N, Ferlin WG, Wu X, Soto H, O'Garra A, Howard MC, Coffman RL (1999) Depletion of eosinophils in mice through the use of antibodies specific for C-C chemokine receptor 3 (CCR3). J Leukoc Biol 65:846
Imai T, Nagira M, Takagi S, Kakizaki M, Nishimura M, Wang J, Gray PW, Matsushima K, Yoshie O (1999) Selective recruitment of CCR4-bearing Th2 cells toward antigen- presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine. Int Immunol 11:81
Zingoni A, Soto H, Hedrick JA, Stoppacciaro A, Storlazzi CT, Sinigaglia F, D'Ambrosio D, O'Garra A, Robinson D, Rocchi M, Santoni A, Zlotnik A, Napolitano M (1998) The chemokine receptor CCR8 is preferentially expressed in Th2 but not Th1 cells. J Immunol 161:547
Siveke J, Hamann A (1998) Cutting edge: Th1 and Th2 cells respond differentially to chemokines. J Immunol 160:550
Jourdan P, Abbal C, Nora N, Hori T, Uchiyama T, Vendrell JP, Bousquet J, Taylor N, Pene J, Yssel H (1998) IL-4 induces functional cell-surface expression of CXCR4 on human T cells. J Immunol 160:4153
Galli G, Annunziato F, Mavilia C, Romagnani P, Cosmi L, Manetti R, Pupilli C, Maggi E, Romagnani S (1998) Enhanced HIV expression during Th2-oriented responses explained by the opposite regulatory effect of IL-4 and IFN-γ of fusin/CXCR4. Eur J Immunol 28:3280
Nagata K, Tanaka K, Ogawa K, Kemmotsu K, Imai T, Yoshie O, Abe H, Tada K, Nakamura M, Sugamura K, Takano S (1999) Selective expression of a novel surface molecule by human Th2 cells in vivo. J Immunol 162:1278
Loetscher M, Loetscher P, Brass N, Meese E, Moser B (1998) Lymphocyte-specific chemokine receptor CXCR3: regulation, chemokine binding and gene localization. Eur J Immunol 28:3696
Loetscher P, Uguccioni M, Bordoli L, Baggiolini M, Moser B, Chizzolini C, Dayer JM (1998) CCR5 is characteristic of Th1 lymphocytes. Nature 391:344
Wu L, Paxton WA, Kassam N, Ruffing N, Rottman JB, Sullivan N, Choe H, Sodroski J, Newman W, Koup RA, Mackay CR (1997) CCR5 levels and expression pattern correlate with infectability by macrophage-tropic HIV-1, in vitro. J Exp Med 185:1681
Loetscher P, Seitz M, Baggiolini M, Moser B (1996) Interleukin-2 regulates CC chemokine receptor expression and chemotactic responsiveness in T lymphocytes. J Exp Med 184:569
Jinquan T, Quan S, Feili G, Larsen CG, Thestrup Pedersen K (1999) Eotaxin activates T cells to chemotaxis and adhesion only if induced to express CCR3 by IL-2 together with IL-4. J Immunol 162:4285
Patterson BK, Czerniewski M, Andersson J, Sullivan Y, Su F, Jiyamapa D, Burki Z, Landay A (1999) Regulation of CCR5 and CXCR4 expression by type 1 and type 2 cytokines: CCR5 expression is downregulated by IL-10 in CD4-positive lymphocytes. Clin Immunol 91:254
Sallusto F, Lenig D, Mackay CR, Lanzavecchia A (1998) Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J Exp Med 187:875
Sallusto F, Kremmer E, Palermo B, Hoy A, Ponath P, Qin S, Forster R, Lipp M, Lanzavecchia A (1999) Switch in chemokine receptor expression upon TCR stimulation reveals novel homing potential for recently activated T cells. Eur J Immunol 29:2037
D'Ambrosio D, Iellem A, Bonecchi R, Mazzeo D, Sozzani S, Mantovani A, Sinigaglia F (1998) Selective up-regulation of chemokine receptors CCR4 and CCR8 upon activation of polarized human type 2 Th cells. J Immunol 161:5111
Teran LM, Mochizuki M, Bartels J, Valencia EL, Nakajima T, Hirai K, Schroder JM (1999) Th1- and Th2-type cytokines regulate the expression and production of eotaxin and RANTES by human lung fibroblasts. Am J Respir Cell Mol Biol 20:777
Schrum S, Probst P, Fleischer B, Zipfel PF (1996) Synthesis of the CC-chemokines MIP-1alpha, MIP-1beta, and RANTES is associated with a type 1 immune response. J Immunol 157:3598
Cole KE, Strick CA, Paradis TJ, Ogborne KT, Loetscher M, Gladue RP, Lin W, Boyd JG, Moser B, Wood DE, Sahagan BG, Neote K (1998) Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3. J Exp Med 187:2009
Lingnau K, Hoehn P, Kerdine S, Koelsch S, Neudoerfl C, Palm N, Ruede E, Schmitt E (1998) IL-4 in combination with TGF-beta favors an alternative pathway of Th1 development independent of IL-12. J Immunol 161:4709
Gunthert U (1999) Importance of CD44 variant isoforms in mouse models for inflammatory bowel disease. Curr Top Microbiol Immunol 246:307
Romagnani S, Parronchi P, D'Elios MM, Romagnani P, Annunziato F, Piccinni MP, Manetti R, Sampognaro S, Mavilia C, De Carli M, Maggi E, Del Prete GF (1997) An update on human Th1 and Th2 cells. Int Arch Allergy Immunol 113:153
Hamann D, Hilkens CM, Grogan JL, Lens SM, Kapsenberg ML, Yazdanbakhsh M, Lier RA van (1996) CD30 expression does not discriminate between human Th1- and Th2-type T cells. J Immunol 156:1387
Nakamura T, Lee RK, Nam SY, Al Ramadi BK, Koni PA, Bottomly K, Podack ER, Flavell RA (1997) Reciprocal regulation of CD30 expression on CD4+ T cells by IL-4 and IFN-γ. J Immunol 158:2090
Xu D, Chan WL, Leung BP, Huang F, Wheeler R, Piedarafita D, Robinson JH, Liew FY (1998) Selective expression of a stable cell surface molecule on type 2 but not type 1 helper cells. J Exp Med 187:787
Löhning M, Stroehmann A, Coyle AJ, Grogan JL, Lin S, Gutierrez-Ramos J-C, Levinson D, Radbruch A, Kamradt T (1998) T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function. Proc Natl Acad Sci USA 95:6930
Löhning M, Grogan JL, Coyle AJ, Yazdankbakhsh M, Meisel C, Gutierrez-Ramos J-C, Radbruch A, Kamradt T (1999) T1/ST2 expression is enhanced on CD4+ T cells from Schistosome egg-induced granulomas: analysis of Th cell cytokine coexpression ex vivo. J Immunol 162:3882
Lohoff M, Prechtl S, Sommer F, Roellinghoff M, Schmitt E, Gradehandt G, Rohwer P, Stride BD, Cole SP, Deeley RG (1998) A multidrug-resistance protein (MRP)-like transmembrane pump is highly expressed by resting murine T helper (Th) 2, but not Th1 cells, and is induced to equal expression levels in Th1 and Th2 cells after antigenic stimulation in vivo. J Clin Invest 101:703
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 185:825
Szabo SJ, Dighe AS, Gubler U, Murphy KM (1997) Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J Exp Med 185:817
Lobb RR, Hemler ME (1994) The pathophysiologic role of alpha 4 integrins in vivo. J Clin Invest 94:1722
Erle D (1996) Leukocyte recruitment to the lung and airways. In: Peltz G (ed) Leukocyte recruitment in inflammatory disease. Molecular Biology Intelligence Unit, New York. Springer/R.G. Landes Company, Austin, p 141
Issekutz TB (1996) Integrins in the control of tissue-specific leukocyte migration in inflammation. In: Peltz G (ed) Leukocyte recruitment in inflammatory disease. Molecular Biology Intelligence Unit, New York. Springer/R.G. Landes Company, Austin, p 247
Cardarelli PM, Lobl TJ (1996) Peptide inhibitors of beta1-integrins. In: Peltz G (ed) Leukocyte recruitment in inflammatory disease. Molecular Biology Intelligence Unit, New York. Springer/R.G. Landes Company, Austin, p 275
Jaeger JR, Rothlein R (1996) Clinical utility of anti-ICAM-1 antibodies. In: Peltz G (ed) Leukocyte recruitment in inflammatory disease. Molecular Biology Intelligence Unit, New York. Springer/R.G. Landes Company, Austin, p 295
Engelhardt B (1997) Lymphocyte trafficking through the central nervous system. In: Hamann A (ed) Adhesion molecules and chemokines in lymphocyte trafficking. Cell adhesion and communication. Harwood, Chur, p 173
Osborn L (1997) Endothelium and inflammation: molecules and therapeutic prospects. In: Hamann A (ed) Adhesion molecules and chemokines in lymphocyte trafficking. Cell adhesion and communication. Harwood, Chur, p 217
Wolitzki BA (1996) The role of E-selectin and P-selectin in inflammatory diseases. In: Peltz G (ed) Leukocyte recruitment in inflammatory disease. Molecular Biology Intelligence Unit, New York. Springer/R.G. Landes Company, Austin, p 211
Tang T, Frenette PS, Hynes RO, Wagner DD, Mayadas TN (1996) Cytokine-induced meningitis is dramatically attenuated in mice deficient in endothelial selectins. J Clin Invest 97:2485
Schwarz MK, Wells TN (1999) Interfering with chemokine networks — the hope for new therapeutics. Curr Opin Chem Biol 3:407
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Syrbe, U., Siveke, J. & Hamann, A. Th1/Th2 subsets: distinct differences in homing and chemokine receptor expression?. Springer Semin Immunopathol 21, 263–285 (1999). https://doi.org/10.1007/BF00812257
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DOI: https://doi.org/10.1007/BF00812257