Surprising Kinetics of the T cell Response to HY (102.25)

Abstract

Abstract Cooperation of CD4+ and CD8+ T cells is required for the development of primary effector and memory CD8+ T cells following immunization with non-inflammatory immunogens. In this study, we characterized endogenous CD4+ and CD8+ T cell responses to male-specific minor histocompatibility (HY) antigens. We find that male cells are rejected 10–12 days after transfer into female mice of the same strain, and this rejection coincides with the expansion and effector function of CD8+ CTLs to two H-2Db-restricted epitopes. While anti-male CD4+ T cell responses are readily detectable day 5 post-transfer, CD8+ T cell response are not detectable until day 10. The early CD4+ T cell response is not dependent on direct presentation of antigen by donor male cells, but depends on processing and presentation of the male cells by female APC. The primary and recall CD8+ T cell responses and rejection of HY incompatible cells are dependent on a sustained CD4+ T cell response and the absence of this response is not replaced by inflammation or treatment with anti-CD40 agonist Ab. Unexpectedly, HY-specific CD4+ T cells are also capable of efficiently lysing target cells in vivo. The delay in the CD8 effector response can be largely abrogated by depleting T cells from the male inoculum, and we further demonstrate that donor CD8+ T cells in particular suppress or veto the host anti-HY CD8+ T cell responses.