Springer Seminars in Immunopathology

, Volume 21, Issue 3, pp 263–285 | Cite as

Th1/Th2 subsets: distinct differences in homing and chemokine receptor expression?

  • Uta Syrbe
  • Jens Siveke
  • Alf Hamann
Article

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.

Keywords

Immune Response Receptor Expression Effector Cell Chemokine Receptor Cell Subset 

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References

  1. 1.
    Weiner HL (1997) Oral tolerance: immune mechanisms and treatment of autoimmune diseases. Immunol Today 18:335Google Scholar
  2. 2.
    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 20:267Google Scholar
  3. 3.
    Huang L, Soldevilla G, Leeker M, Flavell R, Crispe IN (1994) The liver eliminates T cells undergoing antigen-triggered apoptosis in vivo. Immunity 1:741Google Scholar
  4. 4.
    Mehal WZ, Juedes AE, Crispe IN (1999) Selective retention of activated CD8+ T cells by the normal liver. J Immunol 163:3202Google Scholar
  5. 5.
    Hamann A, Rebstock S (1993) Migration of activated lymphocytes. Curr Top Microbiol Immunol 184:109Google Scholar
  6. 6.
    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 1Google Scholar
  7. 7.
    Gowans JL, Knight EJ (1964) The route of recirculation of lymphocytes in the rat. Proc Roy Soc Lond B 159:257Google Scholar
  8. 8.
    Guy-Grand D, Griscelli C, Vassalli P (1974) The gut associated lymphoid system: nature and properties of the large dividing cells. Eur J Immunol 4:435Google Scholar
  9. 9.
    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 99:1281Google Scholar
  10. 10.
    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 162:5173Google Scholar
  11. 11.
    Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76:301Google Scholar
  12. 12.
    Butcher EC, Picker LJ (1996) Lymphocyte homing and homeostasis. Science 272:60Google Scholar
  13. 13.
    Salmi M, Jalkanen S (1997) How do lymphocytes know where to go: current concepts and enigmas of lymphocyte homing. Adv Immunol 64:139Google Scholar
  14. 14.
    Hamann A (ed) (1997) Adhesion molecules and chemokines in lymphocyte trafficking. Harwood, ChurGoogle Scholar
  15. 15.
    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 87:1037Google Scholar
  16. 16.
    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 92:2345Google Scholar
  17. 17.
    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 385:81Google Scholar
  18. 18.
    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 161:963Google Scholar
  19. 19.
    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 121:655Google Scholar
  20. 20.
    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 184:81Google Scholar
  21. 21.
    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 88:6523Google Scholar
  22. 22.
    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 161:6305Google Scholar
  23. 23.
    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 189:1765Google Scholar
  24. 24.
    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 174:1461Google Scholar
  25. 25.
    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 28:1785Google Scholar
  26. 26.
    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 140:693Google Scholar
  27. 27.
    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 189:1467Google Scholar
  28. 28.
    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 337:179Google Scholar
  29. 29.
    Williams MB, Butcher EC (1997) Homing of naive and memory T lymphocyte subsets to Peyer's patches, lymph nodes, and spleen. J Immunol 159:1746Google Scholar
  30. 30.
    Meeusen ENT, Premier RR, Brandon MR (1996) Tissue-specific migration of lymphocytes: a key role for Th1 and Th2 cells? Immunol Today 17:421Google Scholar
  31. 31.
    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 387:713Google Scholar
  32. 32.
    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 28:2025Google Scholar
  33. 33.
    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 95:258Google Scholar
  34. 34.
    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 188:181Google Scholar
  35. 35.
    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 187:655Google Scholar
  36. 36.
    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 391:799Google Scholar
  37. 37.
    Nagasawa T, Kikutani H, Kishimoto T (1994) Molecular cloning and structure of a pre-B-cell growthstimulating factor. Proc Natl Acad Sci USA 91:2305Google Scholar
  38. 38.
    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 162:2472Google Scholar
  39. 39.
    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 141:1053Google Scholar
  40. 40.
    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 10:901Google Scholar
  41. 41.
    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 28:1516Google Scholar
  42. 42.
    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 189:451Google Scholar
  43. 43.
    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 93:3610Google Scholar
  44. 44.
    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 189:403Google Scholar
  45. 45.
    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 189:1461Google Scholar
  46. 46.
    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 27:1788Google Scholar
  47. 47.
    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 184:1101Google Scholar
  48. 48.
    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 94:1925Google Scholar
  49. 49.
    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.Google Scholar
  50. 50.
    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 95:9448Google Scholar
  51. 51.
    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 283:845Google Scholar
  52. 52.
    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 163:1537Google Scholar
  53. 53.
    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 4:648Google Scholar
  54. 54.
    McManus CM, Brosnan CF, Berman JW (1998) Cytokine induction of MIP-1 alpha and MIP-1 beta in human fetal microglia. J Immunol 160:1449Google Scholar
  55. 55.
    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 48:502Google Scholar
  56. 56.
    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 175:478Google Scholar
  57. 57.
    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 162:4928Google Scholar
  58. 58.
    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 162:3549Google Scholar
  59. 59.
    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 160:60Google Scholar
  60. 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 162:2477Google Scholar
  61. 61.
    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 161:5027Google Scholar
  62. 62.
    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 92:2668Google Scholar
  63. 63.
    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 4:1Google Scholar
  64. 64.
    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 98:2332Google Scholar
  65. 65.
    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 67:2590Google Scholar
  66. 66.
    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 101:1693Google Scholar
  67. 67.
    Didier PJ, Paradis TJ, Gladue RP (1999) The CC chemokine MIP-lalpha induces a selective monocyte infiltration following intradermal injection into nonhuman primates. Inflammation 23:75Google Scholar
  68. 68.
    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 9:521Google Scholar
  69. 69.
    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 87:1423Google Scholar
  70. 70.
    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 177:1809Google Scholar
  71. 71.
    Deng W, Ohmori Y, Hamilton TA (1994) Mechanisms of IL-4-mediated suppression of IP-10 gene expression in murine macrophages. J Immunol 153:2130Google Scholar
  72. 72.
    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 154:1870Google Scholar
  73. 73.
    Ohmori Y, Hamilton TA (1998) STAT6 is required for the anti-inflammatory activity of interleukin-4 in mouse peritoneal macrophages. J Biol Chem 273:29202Google Scholar
  74. 74.
    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 11:1001Google Scholar
  75. 75.
    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 188:2225Google Scholar
  76. 76.
    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 162:3193Google Scholar
  77. 77.
    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 185:573Google Scholar
  78. 78.
    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 181:747Google Scholar
  79. 79.
    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 161:1140Google Scholar
  80. 80.
    Murphy KM (1998) T lymphocyte differentiation in the periphery. Curr Opin Immunol 10:226Google Scholar
  81. 81.
    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 159:6018Google Scholar
  82. 82.
    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 189:423Google Scholar
  83. 83.
    Sallusto F, Mackay CR, Lanzavecchia A (1997) Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Science 277:2005Google Scholar
  84. 84.
    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 7:836Google Scholar
  85. 85.
    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 187:129Google Scholar
  86. 86.
    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. 187:875Google Scholar
  87. 87.
    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 65:691Google Scholar
  88. 88.
    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 65:846Google Scholar
  89. 89.
    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 11:81Google Scholar
  90. 90.
    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 161:547Google Scholar
  91. 91.
    Siveke J, Hamann A (1998) Cutting edge: Th1 and Th2 cells respond differentially to chemokines. J Immunol 160:550Google Scholar
  92. 92.
    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 160:4153Google Scholar
  93. 93.
    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 28:3280Google Scholar
  94. 94.
    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 162:1278Google Scholar
  95. 95.
    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 28:3696Google Scholar
  96. 96.
    Loetscher P, Uguccioni M, Bordoli L, Baggiolini M, Moser B, Chizzolini C, Dayer JM (1998) CCR5 is characteristic of Th1 lymphocytes. Nature 391:344Google Scholar
  97. 97.
    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 185:1681Google Scholar
  98. 98.
    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 184:569Google Scholar
  99. 99.
    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 162:4285Google Scholar
  100. 100.
    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 91:254Google Scholar
  101. 101.
    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 187:875Google Scholar
  102. 102.
    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 29:2037Google Scholar
  103. 103.
    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 161:5111Google Scholar
  104. 104.
    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 20:777Google Scholar
  105. 105.
    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 157:3598Google Scholar
  106. 106.
    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 187:2009Google Scholar
  107. 107.
    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 161:4709Google Scholar
  108. 108.
    Gunthert U (1999) Importance of CD44 variant isoforms in mouse models for inflammatory bowel disease. Curr Top Microbiol Immunol 246:307Google Scholar
  109. 109.
    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 113:153Google Scholar
  110. 110.
    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 156:1387Google Scholar
  111. 111.
    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 158:2090Google Scholar
  112. 112.
    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 187:787Google Scholar
  113. 113.
    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 95:6930Google Scholar
  114. 114.
    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 162:3882Google Scholar
  115. 115.
    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 101:703Google Scholar
  116. 116.
    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
  117. 117.
    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 185:817Google Scholar
  118. 118.
    Lobb RR, Hemler ME (1994) The pathophysiologic role of alpha 4 integrins in vivo. J Clin Invest 94:1722Google Scholar
  119. 119.
    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 141Google Scholar
  120. 120.
    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 247Google Scholar
  121. 121.
    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 275Google Scholar
  122. 122.
    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 295Google Scholar
  123. 123.
    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 173Google Scholar
  124. 124.
    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 217Google Scholar
  125. 125.
    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 211Google Scholar
  126. 126.
    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 97:2485Google Scholar
  127. 127.
    Schwarz MK, Wells TN (1999) Interfering with chemokine networks — the hope for new therapeutics. Curr Opin Chem Biol 3:407Google Scholar

Copyright information

© Springer-Verlag 1999

Authors and Affiliations

  • Uta Syrbe
    • 1
    • 2
  • Jens Siveke
    • 1
    • 2
  • Alf Hamann
    • 1
    • 2
  1. 1.Experimentelle Rheumatologie, Medizinische Klinik, CharitéHumboldt-Universität zu BerlinGermany
  2. 2.Demsches RheumaforschungszentrumBerlinGermany

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