Inflammatory cytokines as a third signal for T cell activation

• Published in: Current opinion in immunology 2010-06, Vol.22 (3), p.333-340
• Main Authors: Curtsinger, Julie M, Mescher, Matthew F
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; Cytokines - biosynthesis; Cytokines - immunology; Gene Expression Regulation - immunology; Humans; Inflammation - immunology; Inflammation - metabolism; Lymphocyte Activation - immunology; Mice; Signal Transduction; T-Lymphocytes - cytology; T-Lymphocytes - immunology
• ISSN: 0952-7915; 1879-0372
• DOI: 10.1016/j.coi.2010.02.013

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 (IFNα/β) 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.