IFN-alpha beta and self-MHC divert CD8 T cells into a distinct differentiation pathway characterized by rapid acquisition of effector functions.
Nonvirus-specific bystander CD8 T cells bathe in an inflammatory environment during viral infections. To determine whether bystander CD8 T cells are affected by these environments, we examined P14, HY, and OT-I TCR transgenic CD8 T cells sensitized in vivo by IFN-alphabeta-inducing viral infections or by polyinosinic:polycytidylic acid. These sensitized cells rapidly exerted effector functions, such as IFN-gamma production and degranulation, on contact with their high-affinity cognate Ag. Sensitization required self-MHC I and indirect effects of IFN-alphabeta, which together upregulated the T-box transcription factor Eomesodermin, potentially enabling the T cells to rapidly transcribe CTL effector genes and behave like memory cells rather than naive T cells. IL-12, IL-15, IL-18, and IFN-gamma were not individually required for sensitization to produce IFN-gamma, but IL-15 was required for upregulation of granzyme B. These experiments indicate that naive CD8 T cells receive signals from self-MHC and IFN-alphabeta and that, by this process, CD8 T cell responses to viral infection can undergo distinct differentiation pathways, depending on the timing of Ag encounter during the virus-induced IFN response.
Marshall
Heather D
HD
Department of Pathology, Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Prince
Amanda L
AL
Berg
Leslie J
LJ
Welsh
Raymond M
RM
D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology; D001324:Autoantigens / Q000502:physiology*; D024201:Bystander Effect / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology*; D005260:Female; D006182:H-Y Antigen / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D016898:Interferon-alpha / Q000502:physiology*; D016899:Interferon-beta / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018052:Pichinde virus / Q000276:immunology; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D001324:Autoantigens; D006182:H-Y Antigen; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; D016899:Interferon-beta