Type I IFNs provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation.
In this study, we show that IFN-alpha beta can have a direct role in linking innate and adaptive responses by providing the "third signal" needed by naive CD8 T cells responding to Ag and costimulatory ligands. Stimulation of CD8 T cells in the absence of a third signal leads to proliferation, but clonal expansion is limited by poor survival and effector functions do not develop. We show that IFN-alpha beta can provide the third signal directly to CD8 T cells via a STAT4-dependent pathway to stimulate survival, development of cytolytic function, and production of IFN-gamma. Provision of the third signal by either IFN-alpha beta or IL-12 results in regulation of the expression of a number of genes, including several that encode proteins critical for effector function.
Curtsinger
Julie M
JM
Department of Laboratory Medicine & Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
Valenzuela
Javier O
JO
Agarwal
Pujya
P
Lins
Debra
D
Mescher
Matthew F
MF
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology* / Q000494:pharmacology; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011994:Recombinant Proteins; D050797:STAT4 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000276:immunology
D016207:Cytokines; D004268:DNA-Binding Proteins; D007370:Interferon Type I; D011994:Recombinant Proteins; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12