Programming for a CD8 T Cell Memory Response Requires IL-12 and/or Type I IFN (95.23)

Abstract

Abstract Naïve CD8 T cells proliferate in response to Ag and costimulation, but require signals from IL-12 or IFNα/β to make a productive response. Whether these are the only cytokines with this activity, and their relative contributions, are only beginning to be defined. Response to LCMV infection by CD8 cells lacking the IFNα/β receptor (IFNIR−/−) is reduced > 99%, but response to vaccinia virus (VV) remains largely intact (J.Exp.Med. 202, 637; J. Immunol. 176, 4225). We have studied responses of OT-I T cells to OVA-expressing VV and Listeria monocytogenes (LM), using cells that lack IFNIR, IL-12 receptor (IL-12R−/−), or both (DblKO). Clonal expansion of receptor-deficient OT-I cells to LM-OVA or VV-OVA is comparable to that of wild type (wt) cells, but effector functions are compromised, and their numbers decline more rapidly. IL-12R−/− cells exhibit greater defects than do IFN-IR−/− cells, and DblKO cells are the most compromised. Compared to the wt memory population following VV-OVA infection (> day 30), memory cell numbers are reduced by 27% for IFN-IR−/− cells, 96% for IL-12R−/− cells, and >99% for DblKO cells. For LM-OVA, the reduction in memory is 76% for IFN-IR−/− cells, 97% for IL-12R−/− cells, and >99% for DblKO cells. Thus, both IL-12 and IFNα/β contribute to responses to VV and LM, with IL-12 making the greater contribution, and programming for CD8 T cell memory requires signals from one or the other of these cytokines.