IFN-alpha beta and self-MHC divert CD8 T cells into a distinct differentiation pathway characterized by rapid acquisition of effector functions
Department of Pathology
Medical Subject Headings
Animals; Arenaviridae Infections; Autoantigens; Bystander Effect; CD8-Positive T-Lymphocytes; Cell Differentiation; Female; G0 Phase; H-Y Antigen; Histocompatibility Antigens Class I; Interferon-alpha; Interferon-beta; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Pichinde virus; Signal Transduction; Up-Regulation
Cellular and Molecular Physiology | Immunology and Infectious Disease
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.
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Citation: J Immunol. 2010 Aug 1;185(3):1419-28. doi: 10.4049/jimmunol.1001140.
DOI of Published Version
Journal of immunology (Baltimore, Md. : 1950)
Marshall, Heather D.; Prince, Amanda L.; Berg, Leslie J.; and Welsh, Raymond M., "IFN-alpha beta and self-MHC divert CD8 T cells into a distinct differentiation pathway characterized by rapid acquisition of effector functions" (2010). GSBS Student Publications. 1832.