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Curr Opin Immunol. 2010 Jun;22(3):333-40. doi: 10.1016/j.coi.2010.02.013. Epub 2010 Apr 2.

Inflammatory cytokines as a third signal for T cell activation.

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Center for Immunology, Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN 55455, USA.


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.

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