Checkpoints in the Regulation of T Helper 1 Responses
The immune system has developed to be highly specialized and effective in eradicating a wide variety of pathogens with a minimum of immunopathology. The adaptive arm of the immune response, consisting of antigen-specific T and B cells, interacts with cells of the innate immune system to mediate an effective response to infectious pathogens. Heterogeneity of T cell responses to pathogens can determine the resistance or susceptibility to such infectious agents. In this regard, at least two subsets of CD4+ T helper subsets have been identified; these subsets are characterized by the cytokines they produce and play distinct roles in fighting infection as well as contributing to immunopathology (Mosmann et al. 1986; Romagnani 1991; Sher and Coffman 1992; Abbas 1996). T helper (Th)1 cells produce interferon (IFN)-γ and lymphotoxin and play a critical role in cell-mediated immunity (Mosmann et al. 1986; Sher and Coffman 1992). These cells have also been implicated as being involved in organ-specific autoimmune diseases, such as multiple sclerosis and insulin-dependent diabetes, as well as chronic inflammatory diseases including inflammatory bowel disease (Powrie and Coffman 1993; Liblau et al. 1995; O’Garra 1998). Th2 cells produce interleukin (IL)-4, IL-5, IL-10, and IL-13 and are important in helminth immunity, as well as playing a role in allergy and atopy (Romagnani 1994; O’Garra 1998). Gaining an understanding of the molecular mechanisms of Th1 and Th2 development is critical both for the development of more powerful anti-microbial agents as well as for the development of therapies for immunopathologies.
KeywordsFlow Cytometric Cell Sorting ofTh2 Cell DNAX Research Institute
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- Bohn E, Sing A, Zumbihl R, Bielfeldt C, Okamura H, Kurimoto M, Heesemann JGoogle Scholar
- Gery I, Lepe-Zuniga JL (1983) Interleukin 1. Lymphokines 9: 109–126Google Scholar
- Ho IC, Lo D, Glimcher LH (1998) c-maf promotes T helper cell type 2 (Th2) and attenuates Thl differentiation by both interleukin 4-dependent and -independent mechanisms. J Exp Med 188: 1859–1866Google Scholar
- Hunter CA, Timans J, Pisacane P, Menon S, Cai G, Chizzonitte R, Bazan JF, Kastelein RA (1997) Comparison of the effects of interleukin-la Interleukin-113 and Interferon-7 inducing factor on the production of interferon-7 by natural killer cells. Eur J Immunol 27: 2787–2792PubMedCrossRefGoogle Scholar
- Jacobson NG, Szabo SJ, Weber-Nordt RM, Zhong Z, Schreiber RD, Darnell JEJ, Murphy KM (1995) Interleukin 12 signalling in T helper type 1 (Thl) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (stat)3 and Stat4. J Exp Med 181: 1755–1762PubMedCrossRefGoogle Scholar
- Kamogawa Y, Lee HJ, Johnston JA, McMahon M, O’Garra A, Arai N (1998) A conditionally active form of STAT6 can mimic certain effects of 1L-4. J Immunol 161: 10741077Google Scholar
- Manetti R, Parronchi P, Guidizi MG, Piccinni M-P, Maggi E, Trinchieri G, Romagnani S (1993) Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing cells. J Exp Med 177: 1199–1204PubMedCrossRefGoogle Scholar
- Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136: 2348–2357Google Scholar
- Quelle FW, Shimoda K, Thierfelder W, 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: 3336–3343PubMedGoogle Scholar
- Sims JE, March CJ, Cosman D, Widmer MB, MacDonald HR, McMahan CJ, Grubin CE, Wignall JM, Jackson JL, Call SM, et al. (1988) cDNA expression cloning of the IL-1 receptor a member of the immunoglobulin superfamily. Science 241: 585–589Google Scholar
- Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH (2000) A novel transcription factor, T-bet, directs Thl lineage commitment. Cell 655–669Google Scholar