| First Author | Marshall HD | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 3 | Pages | 1419-28 |
| PubMed ID | 20592282 | Mgi Jnum | J:162457 |
| Mgi Id | MGI:4819020 | Doi | 10.4049/jimmunol.1001140 |
| Citation | Marshall HD, et al. (2010) IFN-alphabeta and self-MHC divert CD8 T cells into a distinct differentiation pathway characterized by rapid acquisition of effector functions. J Immunol 185(3):1419-28 |
| abstractText | 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. |
