Inflammatory cytokines as a third signal for T cell activation.
CD8 T cells require a third signal, along with Ag and costimulation, to make a productive response and avoid death and/or tolerance induction. Recent studies indicate that IL-12 and Type I IFN (IFNalpha/beta) are the major sources of signal 3 in a variety of responses, and that the two cytokines stimulate a common regulatory program involving altered expression of about 350 genes. Signal 3-driven chromatin remodeling is likely to play a major role in this regulation. Although less well studied, there is emerging evidence that CD4 T cells may also require a 'third signal' for a productive response and that IL-1 can provide this signal. Signal 3 cytokines can replace adjuvants in supporting in vivo T cell responses to peptide and protein antigens, and a better understanding of their activities and mechanisms should contribute to more rational design of vaccines.
Curtsinger
Julie M
JM
Center for Immunology, Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Mescher
Matthew F
MF
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D016207:Cytokines