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The role of Th1/Th2 polarization in mucosal immunity

Abstract

Mucosal immunity relies on the delicate balance between antigen responsiveness and tolerance. The polarization of T helper cells plays a key role in maintaining or disrupting this equilibrium.

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Figure 1: Inductive sites of the MALT: Whereas the NALT appears to be the major inductive site for mucosal immunity to inhaled antigens, the GALT (for example, Peyer's patches in the small bowel and colonic follicles in the large bowel) is the major inductive site for the gastrointestinal tract.

Renee Lucas

Figure 2: Cytokine production by mucosal T-helper cells in response to antigens.

Renee Lucas

Figure 3: Induction of pathogenic Th1 and Th2 immune responses at effector sites of the mucosal immune system using Th1-dependent chronic intestinal inflammation and Th2-dependent airway/lung inflammation as examples.

Renee Lucas

Figure 4: Cytokine signaling in T lymphocytes via IFN-γ, IL-12 and IL-4.

Renee Lucas

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References

  1. Elson, C.O., R.B. Sartor, G.S. Tennyson & R.H. Riddell. Experimental models of inflammatory bowel disease. Gastroenterology 109, 1344–1367 (1995).

    Article  CAS  PubMed  Google Scholar 

  2. Wills-Karp, M. et al. Interleukin-13: central mediator of allergic asthma. Science 282, 2258–2261 (1998).

    Article  CAS  PubMed  Google Scholar 

  3. Strober, W. et al. Reciprocal IFN-γ and TGF-β responses regulate the occurrence of mucosal inflammation. Immunol. Today 18, 61–64 (1997).

    Article  CAS  PubMed  Google Scholar 

  4. Elias, J.A., Zhu, G., Chupp, Z. & Homer, R.J. Airway remodeling in asthma. J. Clin. Invest. 104, 1001–1006 (1999).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Maloy, K.J. & F. Powrie. Regulatory T cells in the control of immune pathology. Nature Immunol. 2, 816–822 (2001).

    Article  CAS  Google Scholar 

  6. Jong, Y.P. et al. Development of chronic colitis is dependent on the cytokine MIF. Nature Immunol. 2, 1061–1066 (2001).

    Article  CAS  Google Scholar 

  7. Podolsky, D.K. Mucosal immunity and inflammation. V. Innate mechanisms of mucosal defense and repair: the best offense is a good defense. Am. J. Physiol. 277, G495–499 (1999).

    CAS  PubMed  Google Scholar 

  8. Blumberg, R.S., Saubermann, L.J. & Strober, W. Animal models of mucosal inflammation and their relation to human inflammatory bowel disease. Curr. Opin. Immunol. 11, 648–656 (1999).

    Article  CAS  PubMed  Google Scholar 

  9. Weiner, H.L. Oral tolerance: immune mechanisms and the generation of Th3-type TGF-β-secreting regulatory cells. Microbes Infect. 3, 947–954 (2001).

    Article  CAS  PubMed  Google Scholar 

  10. Akbari, O., DeKruyff, R.H. & Umetsu, D.T. Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nature Immunol. 2, 725–731 (2001).

    Article  CAS  Google Scholar 

  11. Kelsall, B. & Strober, W. Gut-associated lymphoid tissue: antigen handling and T lymphocyte responses. in Mucosal Immunology (ed. Ogra,P.L.) 293–318 (Academic Press, San Diego, 1999).

    Google Scholar 

  12. Shanahan, F. Crohn's disease. Lancet 359, 62–69 (2002).

    Article  CAS  PubMed  Google Scholar 

  13. Hugot, J.P. et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411, 599–603 (2001).

    Article  CAS  PubMed  Google Scholar 

  14. Ogura, Y. et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411, 603–6 (2001).

    Article  CAS  PubMed  Google Scholar 

  15. Wills-Karp, M. Asthma genetics: not for the TIMid? Nature Immunol. 2, 1095–1096 (2001).

    Article  CAS  Google Scholar 

  16. Powrie, F. et al. Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells. Immunity 2, 553–562 (1994).

    Article  Google Scholar 

  17. Mombaerts, P. et al. Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell 75, 275–282 (1993).

    Article  CAS  Google Scholar 

  18. Mizoguchi, A., Mizoguchi, E. & Bhan, A.K. The critical role for interleukin-4 but not interferon-γ in the pathogenesis of colitis in T-cell receptor α mutant mice. Gastroenterology 116, 320–326 (1999).

    Article  CAS  PubMed  Google Scholar 

  19. Lee, N.A., Gelfand, E.W. & Lee, J.J. Pulmonary T cells and eosinophils: coconspirators or independent triggers of allergic respiratory pathology? J. Allergy Clin. Immunol. 107, 945–957 (2001).

    Article  CAS  PubMed  Google Scholar 

  20. Hansen, G. et al. CD4(+) T helper cells engineered to produce latent TGF-β1 reverse allergen-induced airway hyperreactivity and inflammation. J. Clin. Invest. 105, 61–70 (2000).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Wirtz, S. et al. Cutting edge: Chronic intestinal inflammation in STAT-4 transgenic mice: Characterization of disease and adoptive transfer by TNF- plus IFN-γ producing CD4+ T cells that respond to bacterial antigens. J. Immunol. 162, 1884–1888 (1999).

    CAS  PubMed  Google Scholar 

  22. Boirivant, M., Fuss, I.J., Chu, A. & Strober, W. Oxazolone colitis: a murine model of T helper cell type 2 colitis treatable with antibodies to interleukin-4. J. Exp. Med. 188, 1929–1939 (1998).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Atreya, R. et al. Blockade of IL-6 trans-signaling suppresses T cell resistance against apoptosis in chronic intestinal inflammation: Evidence in Crohn's disease and experimental colitis in vivo. Nature Med. 6, 583–588 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Simpson, S.J. et al. T cell–mediated pathology in two models of experimental colitis depends predominantly on the interleukin 12/Signal transducer and activator of transcription (Stat)-4 pathway, but is not conditional on interferon γ expression by T cells. J. Exp. Med. 187, 1225–1234 (1998).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Iqbal, N. et al. T helper 1 and T helper 2 cells are pathogenic in an antigen-specific model of colitis. J. Exp. Med. (in the press).

  26. Powrie, F., Carlino, J., Leach, M.W., Mauze, S. & Coffman, R.L. A critical role for transforming growth factor-β but not interleukin-4 in the suppression of T helper type 1-mediated colitis by CD45Rb(low) CD4+ T cells. J. Exp. Med. 183, 2669–2674 (1996).

    Article  CAS  PubMed  Google Scholar 

  27. Asseman, C., Mauze, S., Leach, M.W., Coffman, R.L. & Powrie, F. An essential role for interleukin-10 in the function of regulatory T cells that inhibit intestinal inflammation. J. Exp. Med. 190, 995–1003 (1999).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Fuss, I. et al. Disparate CD4+ lamina propria (LP) lymphocyte secretion profiles in inflammatory bowel disease. J. Immunol. 157, 1261–1270 (1996).

    CAS  PubMed  Google Scholar 

  29. Glimcher, L.H. & Murphy, K.M. Lineage commitment in the immune system: the T helper lymphocyte grows up. Genes Dev. 14, 1693–1711 (2000).

    CAS  PubMed  Google Scholar 

  30. Mosmann, T.R. & Sad, S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol. Today 17, 138–146 (1996).

    Article  CAS  PubMed  Google Scholar 

  31. Moser, M. & Murphy, K.M. Dendritic cell regulation of TH1-TH2 development. Nature Immunol. 1, 199–205 (2000).

    Article  CAS  Google Scholar 

  32. Liu, Z. et al. B7 interactions with CD28 and CTLA-4 control tolerance or induction of mucosal inflammation in chronic experimental colitis. J. Immunol. 167, 1830–1838 (2001).

    Article  CAS  PubMed  Google Scholar 

  33. Jember, A.G., Zuberi, R., Liu, F.T. & Croft, M. Development of allergic inflammation in a murine model of asthma is dependent on the costimulatory receptor OX40. J. Exp. Med. 193, 387–392 (2001).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Higgins, L.M. et al. Regulation of T cell activation in vitro and in vivo by targeting the OX40–OX40 ligand interaction: amelioration of ongoing inflammatory bowel disease with an OX40–IgG fusion protein, but not with an OX40 ligand-IgG fusion protein. J. Immunol. 162, 186–493 (1999).

    Google Scholar 

  35. Tesciuba, A.G. et al. Inducible costimulator regulates Th2-mediated inflammation, but not Th2 differentiation, in a model of allergic airway disease. J. Immunol. 167, 1996–2003 (2001).

    Article  CAS  PubMed  Google Scholar 

  36. Romagnani, S. The Th1/Th2 paradigm. Immunol. Today 18, 263–266 (1997).

    Article  CAS  PubMed  Google Scholar 

  37. Dinarello, C.A. IL-18: a Th1-inducing pro-inflammatory cytokine and new member of the IL-1 family. J. Allergy Clin. Immunol. 103, 11–19 (1999).

    Article  CAS  PubMed  Google Scholar 

  38. Barbulescu, K. et al. Cutting edge: Interleukin-12 and interleukin-18 differentially regulate the transcriptional activity of the human IFN-γ promoter in primary CD4+ T lymphocytes. J. Immunol. 160, 3642–3647 (1998).

    CAS  PubMed  Google Scholar 

  39. Akira, S. The role of IL-18 in innate immunity. Curr. Opin. Immunol. 12, 59–63 (2000).

    Article  CAS  PubMed  Google Scholar 

  40. Wills-Karp, M. Immunologic basis of antigen-induced airway hyperresponsiveness. Annu. Rev. Immunol. 17, 255–281 (1999).

    Article  CAS  PubMed  Google Scholar 

  41. Pulendran, B., Maraskovsky, E., Banchereau, J. & Maliszewski, C. Modulating the immune response with dendritic cells and their growth factors. Trends Immunol. 22, 41–47 (2001).

    Article  CAS  PubMed  Google Scholar 

  42. Iwasaki, A. & Kelsall, B.L. Freshly isolated Peyer's patch, but not spleen, dendritic cells produce interleukin 10 and induce the differentiation of T helper type 2 cells. J. Exp. Med. 190, 229–239 (1999).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Stumbles, P.A. et al. Resting respiratory tract dendritic cells preferentially stimulate T helper cell type 2 (Th2) responses and require obligatory cytokine signals for induction of Th1 immunity. J. Exp. Med. 188, 2019–2031 (1998).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Rengarajan, J. & Szabo, S.J. Transcriptional regulation of Th1/Th2 polarization. Immunol. Tod. 21, 479–483 (2000).

    Article  CAS  Google Scholar 

  45. Grogan, J.L. et al. Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets. Immunity 14, 205–215 (2001).

    Article  CAS  PubMed  Google Scholar 

  46. Rao, A., Luo, C. & Hogan, P.G. Transcription factors of the NFAT family: regulation and function. Annu. Rev. Immunol. 15, 707–747 (1997).

    Article  CAS  PubMed  Google Scholar 

  47. Asnagli, H. & Murphy, K.M. Stability and commitment in T helper cell development. Curr. Opin. Immunol. 13, 242–247 (2001).

    Article  CAS  PubMed  Google Scholar 

  48. Magram, J. et al. IL-12-deficient mice are defective in IFN-γ production and type 1 cytokine responses. Immunity 4, 471–481 (1996).

    Article  CAS  PubMed  Google Scholar 

  49. Szabo, S.J., Jacobson, N.G., Dighe, A.S., Gubler, U. & Murphy, K.M. Developmental commitment to the Th2 lineage by extinction of IL-12 signaling. Immunity 2, 665–675 (1995).

    Article  CAS  PubMed  Google Scholar 

  50. Neurath, M.F., Fuss, I., Kelsall, B.L., Stuber E. & Strober, W. Antibodies to IL-12 abrogate established experimental colitis in mice. J. Exp. Med. 182, 1280–1289 (1995).

    Article  Google Scholar 

  51. Fuss, I.J. et al. Anti-interleukin 12 treatment regulates apoptosis of Th1 T cells in experimental colitis in mice. Gastroenterology 117, 1078–1088 (1999).

    Article  CAS  PubMed  Google Scholar 

  52. Davidson, N.J. et al. IL-12, but not IFN-γ, plays a major role in sustaining the chronic phase of colitis in IL-10-deficient mice. J. Immunol. 161, 3143–3149 (1998).

    CAS  PubMed  Google Scholar 

  53. Oppmann, B. et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biologic activities similar as well as distinct from IL-12. Immunity 13, 715–725 (2000).

    Article  CAS  PubMed  Google Scholar 

  54. Wiekowski, M.T. et al. Ubiquitous transgenic expression of the IL-23 subunit p19 induces multiorgan inflammation, runting, infertility, and premature death. J. Immunol. 166, 7563–7570 (2001).

    Article  CAS  PubMed  Google Scholar 

  55. Hove, T.T. et al. Blockade of endogenous IL-18 ameliorates TNBS-induced colitis by decreasing local TNF-α production in mice. Gastroenterology 121, 1372–1379 (2001).

    Article  CAS  PubMed  Google Scholar 

  56. Kanai, T. et al. Macrophage-derived IL-18-mediated intestinal inflammation in the murine model of crohn's disease. Gastroenterology 121, 875–888 (2001).

    Article  CAS  PubMed  Google Scholar 

  57. Siegmund, B. et al. Neutralization of interleukin-18 reduces severity in murine colitis and intestinal IFN-γ and TNF-α production. Am. J. Physiol. Regul. Integr. Comp. Physiol. 281, 1264–1273 (2001).

    Article  Google Scholar 

  58. Wirtz, S., Becker, C., Blumberg, R., Galle, P.R. & Neurath, M.F. Treatment of T cell–dependent experimental colitis in SCID mice by local administration of an adenovirus expressing IL-18 antisense mRNA. J. Immunol. 168, 411–420 (2002).

    Article  CAS  PubMed  Google Scholar 

  59. Monteleone, G. et al. Interleukin-12 is expressed and actively released by Crohn's disease intestinal lamina propria mononuclear cells. Gastroenterology 112, 1169–1178 (1997).

    Article  CAS  PubMed  Google Scholar 

  60. Pizarro, T.T. et al. IL-18, a novel immunoregulatory cytokine, is upregulated in Crohn's disease: expression and localization in intestinal mucosal cells. J. Immunol. 162, 6829–6835 (1999).

    CAS  PubMed  Google Scholar 

  61. Carter, L.L. & Murphy, K.M. Lineage-specific requirement for signal transducer and activator of transcription Stat4 in interferon-γ production from CD4(+) versus CD8(+) T cells. J. Exp. Med. 189, 1355–1360 (1999).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Durbin, J.E., Hackenmiller, R., Simon, M.C & Levy, D.E. Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease. Cell 84, 443–450 (1996).

    Article  CAS  PubMed  Google Scholar 

  63. Szabo, S.J. et al. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100, 655–669 (2000).

    Article  CAS  PubMed  Google Scholar 

  64. Szabo, S.J. et al. T-bet is Essential for Th1 lineage commitment and IFN-γ production in CD4 but not CD8 T cells. Science 295, 338–342 (2002).

    Article  CAS  PubMed  Google Scholar 

  65. Neurath, M.F. et al. The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease. J. Exp. Med. (in the press).

  66. Mullen, A.C. et al. Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science 292, 1907–1910 (2001).

    Article  CAS  PubMed  Google Scholar 

  67. McIntire, J.J. et al. Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family. Nature Immunol. 2, 1109–1116 (2001).

    Article  CAS  Google Scholar 

  68. Ho, I.C., Hodge, M.R., Rooney, J.W. & Glimcher, L.H. The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4. Cell 85, 973–983 (1996).

    Article  CAS  PubMed  Google Scholar 

  69. Li, B., Tournier, C., Davis, R.J. & Flavell, R.A. Regulation of IL-4 expression by the transcription factor JunB during T helper cell differentiation. EMBO J. 18, 420–432 (1999).

    Article  PubMed Central  PubMed  Google Scholar 

  70. Zheng, W. & Flavell, R.A. The transcription factor GATA-3 is necessary and sufficent for Th2 cytokine gene expression in CD4+ T cells. Cell 89, 587–596 (1997).

    Article  CAS  PubMed  Google Scholar 

  71. Kurata, H., Lee, H.J., O'Garra, A. & Arai, N. Ectopic expression of activated STAT-6 induces the expression of Th2-specific cytokines and transcription factors in developing Th1 cells. Immunity 11, 677–688 (1999).

    Article  CAS  PubMed  Google Scholar 

  72. Ranger, A.M. et al. Delayed lymphoid repopulation with defects in IL-4-driven responses produced by inactivation of NF-ATc. Immunity 8, 125–134 (1998).

    Article  CAS  PubMed  Google Scholar 

  73. Rengarajan, J., Tang, B. & Glimcher, L.H. NFATc2 and NFATc3 regulate TH2 differentiation and modulate TCR-responsiveness of naïve TH cells. Nature Immunol. 3, 48–54 (2002).

    Article  CAS  Google Scholar 

  74. Ho, I.C. et al. Human GATA-3: A lineage-restricted transcription factor that regulates the expression of the T cell receptor α gene. EMBO J. 10, 1187–1191 (1993).

    Article  Google Scholar 

  75. Ouyang, W. et al. Stat-6 independent GATA-3 autoactivation directs IL-4 independent Th2 development and commitment. Immunity 12, 27–37 (2000).

    Article  CAS  PubMed  Google Scholar 

  76. Ouyang, W. et al. Inhibition of Th1 development mediated by GATA-3 through an IL-4 independent mechanism. Immunity 9, 745–755 (1998).

    Article  CAS  PubMed  Google Scholar 

  77. Lee, G.R., Fields, P.E. & Flavell, R.A. Regulation of IL-4 gene expression by distal regulatory elements and GATA-3 at the chromatin level. Immunity 14, 447–459 (2001).

    Article  CAS  PubMed  Google Scholar 

  78. Miaw, S.C., Choi, A., Yu, E., Kishikawa, H. & Ho, I.C. ROG, repressor of GATA, regulates the expression of cytokine genes. Immunity 12, 323–333 (2000).

    Article  CAS  PubMed  Google Scholar 

  79. Lee, H.J. et al. GATA-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin remodeling in committed Th1 cells. J. Exp. Med. 192, 105–115 (2000).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Gelfand, E.W. Essential role of T lymphocytes in the development of allergen-driven airway hyperresponsiveness. Allergy Asthma Proc. 19, 365–369 (1998).

    Article  CAS  PubMed  Google Scholar 

  81. Holgate, S.T. The epidemic of allergy and asthma. Nature 402, B2–B4 (1999).

    Article  CAS  PubMed  Google Scholar 

  82. Tomkinson, A. et al. A murine IL-4 receptor antagonist that inhibits IL-4- and IL-13-induced responses prevents antigen-induced airway eosinophilia and airway hyperresponsiveness. J. Immunol. 166, 5792–5800 (2001).

    Article  CAS  PubMed  Google Scholar 

  83. Zhu, Z. et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities & eotaxin production. J. Clin. Invest. 103, 779–788 (1999).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Zhu, Z. et al. Airway inflammation and remodeling in asthma. Lessons from interleukin 11 and interleukin 13 transgenic mice. Am. J. Respir. Crit. Care Med. 164, S67–70 (2001).

    Article  CAS  PubMed  Google Scholar 

  85. Temann, U.A., Ray, P. & Flavell, R.A. Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology. J. Clin. Invest. 109, 29–39 (2002).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  86. Christodoulopoulos, P. et al. TH2 cytokine-associated transcription factors in atopic and nonatopic asthma: evidence for differential signal transducer and activator of transcription 6 expression. J. Allergy Clin. Immunol. 107, 586–591 (2001).

    Article  CAS  PubMed  Google Scholar 

  87. Akimoto, T. et al. Abrogation of bronchial eosinophilic inflammation and airway hyperreactivity in signal transducers and activators of transcription (STAT)6-deficient mice. J. Exp. Med. 187, 1537–1542 (1998).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  88. Mathew, A. et al. Signal transducer and activator of transcription 6 controls chemokine production and T helper cell type 2 cell trafficking in allergic pulmonary inflammation. J. Exp. Med. 193, 1087–1096 (2001).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  89. Zhang, D.H. et al. Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3. Immunity 11, 473–482 (1999).

    Article  CAS  PubMed  Google Scholar 

  90. Finotto, S. et al. Treatment of allergic airway inflammation and hyperresponsiveness by local antisense-induced blockade of GATA-3 expression. J. Exp. Med. 193, 1247–1260 (2001).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  91. Das, J. et al. A critical role for NF-κB in GATA3 expression and TH2 differentiation in allergic airway inflammation. Nature Immunol. 2, 45–50 (2001).

    Article  CAS  Google Scholar 

  92. Finotto, S. et al. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 295, 336–338 (2002).

    Article  CAS  PubMed  Google Scholar 

  93. Gao, P.S. et al. Variants of STAT6 (signal transducer and activator of transcription 6) in atopic asthma. J. Med. Genet. 37, 380–382 (2000).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  94. Coyle, A.J. et al. Crucial role of the interleukin 1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses. J. Exp. Med. 190, 895–902 (1999).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  95. Lohning, M. et al. 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, 6930–6935 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Barnes, P.J. Cytokine-directed therapies for asthma. J. Allergy Clin. Immunol. 108, S72–76 (2001).

    Article  CAS  PubMed  Google Scholar 

  97. Lighvani, A.A. et al. T-bet is rapidly induced by interferon-γ in lymphoid and myeloid cells. Proc. Natl. Acad. Sci. USA 98, 15137–15142 (2001).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  98. Targan, S.R. et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor α for Crohn's disease. New Engl. J. Med. 337, 1029–1035 (1997).

    Article  CAS  PubMed  Google Scholar 

  99. Borish, L.C. et al. Efficacy of soluble IL-4 receptor for the treatment of adults with asthma. J. Allergy Clin. Immunol. 107, 963–970 (2001).

    Article  CAS  PubMed  Google Scholar 

  100. Busse, W.W. & Lemanske, R.F. Jr. Asthma. N Engl. J. Med. 344, 350–362 (2001).

    Article  CAS  PubMed  Google Scholar 

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Neurath, M., Finotto, S. & Glimcher, L. The role of Th1/Th2 polarization in mucosal immunity. Nat Med 8, 567–573 (2002). https://doi.org/10.1038/nm0602-567

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