A Call to Arms: The Cytokine Selection Service
Abstract
The process by which naïve T helper (TH) cells differentiate into the TH1 and TH2 subtypes has been well studied. However, there remain some unresolved issues pertaining to the requirements for the initial step of TH cell differentiation. Much debate exists about whether the roles of cytokines include the forcing of the initial steps of differentiation on naïve TH cells, termed "instruction," or whether cytokines act in a supportive role, termed "selection," whereby newly differentiating TH cells are given the proper signals for survival and proliferation. A recent paper by Mullen et al., which helps delineate the role of cytokines in TH1 cell development, is addressed by Nelson; it appears that cytokines act in the selection stage of TH cell maturation.
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References
1.
T. R. Mosmann, H. Cherwinski, M. W. Bond, M. A. Giedlin, R. L. Coffman, Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136, 2348-2357 (1986).
2.
A. K. Abbas, K. M. Murphy, A. Sher, Functional diversity of helper T lymphocytes. Nature 383, 787-793 (1996).
3.
A. N. McKenzie, Regulation of T helper type 2 cell immunity by interleukin-4 and interleukin-13. Pharmacol. Ther. 88, 143-151 (2000).
4.
K. J. Else, F. D. Finkelman, Intestinal nematode parasites, cytokines and effector mechanisms. Int. J. Parasitol. 28,1145-1158 (1998).
5.
A. Sher, R. L. Coffman, Regulation of immunity to parasites by T cells and T cell derived cytokines. Annu. Rev. Immunol. 10, 385-409 (1992).
6.
T. R. Mosmann, T lymphocyte subsets, cytokines, and effector functions. Ann. N.Y. Acad. Sci. 664, 89-92 (1992).
7.
K. M. Murphy, W. Ouyang, J. D. Farrar, J. Yang, S. Ranganath, H. Asnagli, M. Afkarian, T. L. Murphy, Signaling and transcription in T helper development. Annu. Rev. Immunol. 18, 451-494 (2000).
8.
L. Rogge, L. Barberis-Maino, M. Biffi, N. Passini, D. H. Presky, U. Gubler, F. Sinigaglia, Selective expression of an interleukin-12 receptor component by human T helper 1 cells. J. Exp. Med. 185, 825-831 (1997).
9.
S. J. Szabo, A. S. Dighe, U. Gubler, K. M. Murphy, Regulation of the interleukin (IL)-12R β2 subunit expression in developing T helper 1 (TH1) and TH2 cells. J. Exp. Med. 185, 817-824 (1997).
10.
J. A. Gollob, H. Kawasaki, J. Ritz, Interferon-gamma and interleukin-4 regulate T cell interleukin-12 responsiveness through the differential modulation of high-affinity interleukin-12 receptor expression. Eur. J. Immunol. 27, 647-652 (1997).
11.
L. H. Glimcher, K. M. Murphy, Lineage commitment in the immune system: the T helper lymphocyte grows up. Genes Dev. 14, 1693-1711 (2000).
12.
S. J. Szabo, S. T. Kim, G. L. Costa, X. Zhang, C. G. Fathman, L. H. Glimcher, A novel transcription factor, T-bet, directs TH1 lineage commitment. Cell 100, 655-669 (2000).
13.
R. L. Coffman, S. L. Reiner, Instruction, selection, or tampering with the odds? Science 284, 1283-1285 (1999).
14.
A. C. Mullen, F. A. High, A. S. Hutchins, H. W. Lee, A. V. Villarino, D. M. Livingston, A. L. Kung, N. Cereb, T. P. Yao, S. Y. Yang, S. L. Reiner, Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science 292, 1907-1910 (2001).
15.
J. L. Grogan, M. Mohrs, B. Harmon, D. A. Lacy, J. W. Sedat, R. M. Locksley, Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets. Immunity 14, 205-215 (2001).
16.
M. H. Kaplan, A. L. Wurster, M. J. Grusby, A signal transducer and activator of transcription (Stat)4-independent pathway for the development of T helper type 1 cells. J. Exp Med. 188, 1191-1196 (1998).
17.
S. Agarwal, A. Rao, Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. Immunity 9, 765-775 (1998).
18.
J. D. Farrar, W. Ouyang, M. Lohning, M. Assenmacher, A. Radbruch, O. Kanagawa, K. M. Murphy, An instructive component in T helper cell type 2 (TH2) development mediated by GATA-3. J. Exp. Med. 193, 643-650 (2001).
19.
V. K. Singh, S. Mehrotra, S. S. Agarwal, The paradigm of TH1 and TH2 cytokines: its relevance to autoimmunity and allergy. Immunol. Res. 20,147-161 (1999).
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Volume 2001 | Issue 91
July 2001
July 2001
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