Innate memory phenotype CD8+ T cells exhibit prompt and potent antigen specific response (46.2)

Abstract

Abstract Innate memory phenotype CD8 T cells (IMP CD8+CD44hiCD122int) develop in thymus and carry abundant preformed mRNA for cytokines such as interferon-γ (IFN-γ). These cells rapidly produce IFN-γ when stimulated with PMA/Ionomycin or IL-12/IL-18. Whether they can also contribute to antigen specific responses is unclear, as it is difficult to distinguish them from “true” memory cells. We developed a novel method to derive antigen specific IMP CD8, using murine bone marrow chimeras to separate naïve and IMP antigen specific CD8 T cells recognizing the model antigen ovalbumin (OVA). WT or OTI bone marrow transplanted into irradiated MHCI-/- mice gave rise to predominantly IMP CD8 T cells. By contrast, MHCI-/- or OTIMHCI-/- bone marrow transplanted into irradiated WT mice gave rise to predominantly naïve CD8 T cells. IMP CD8 T cells thus derived significantly up-regulated IFN-γ 6 days post OVA restimulation in vitro, following primary exposure to transgenic Listeria-OVA, compared to analogously derived naïve CD8 T cells alone or WT controls. More importantly, OTI IMP CD8 T cells exhibited significantly enhanced early response to OVA or OVA257-264 peptide without primary stimulation. Our findings indicate that the dynamics of the antigen specific response of IMP CD8 T cells is enhanced compared to antigen specific naïve CD8 T cells. Furthermore, this work provides a promising murine model for future investigation of IMP CD8 T cell memory development and antigen response.