Differential induction of transcription factors that regulate the interleukin 2 gene during anergy induction and restimulation.
T cell activation requires two distinct signals. The first is delivered through the antigen-specific T cell receptor (TCR), and the second is provided by costimulatory molecule(s) present on the surface of the antigen-presenting cell (APC). Stimulation of T helper type 1 T cell clones through the TCR in the absence of the costimulatory activity results in a lack of interleukin 2 (IL-2) secretion and proliferation, and the induction of a long-lived state of nonresponsiveness, termed anergy. In this study, we have examined the transcription factors involved in IL-2 gene expression that are expressed after stimulation of normal T cell clones through the TCR with and without engagement of the necessary costimulatory molecule(s). Antigen-specific activation of the clones results in the induction of a similar pattern of transcription factors that have been previously shown to regulate IL-2 expression. In contrast, antigen presentation by chemically fixed APC, a condition that results in T cell anergy, induces neither NF-AT nor one of the two NF-kappa B binding factors. Thus, the failure to express IL-2 during the induction of T cell anergy may be attributed to the absence of these two transcription factors. When anergized T cells are restimulated with antigen and conventional APC, they induce the transcription factors associated with IL-2 expression, but they fail to synthesize measurable IL-2. Taken together, these data indicate that the control of IL-2 gene expression during anergy induction and during normal stimulation of anergized cells are distinct, and suggest the presence of additional regulatory elements in the IL-2 gene.
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C
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Department of Pathology, University of Chicago, Illinois 60637.
Miller
J
J
D000818:Animals; D002455:Cell Division; D005786:Gene Expression Regulation; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D007376:Interleukin-2; D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors