Short-term corticosterone treatment decreases the early CD8+ T cell response to simian virus 40 tumor antigen but has no impact on the late CD8+ T cell response

Abstract

CD8+ T cells (T(CD8)) help control tumor growth in vivo through recognition of distinct tumor antigens and cytolysis of tumor cells. The T(CD8) immune response in C57BL/6 mice to the Simian Virus 40 oncoprotein, large tumor antigen (Tag), targets multiple epitopes and is well-characterized. Epitope IV, an H-2K(b)-restricted epitope, is immunodominant while epitope I, an H-2D(b)-restricted epitope is subdominant. GCs alter many aspects of T cell function. Indeed, the current studies demonstrate that exposure of mice to the immunosuppressive GC, corticosterone (CORT), over the entire course of the primary immune response limits activation of endogenous Tag-specific T(CD8). Even short-term CORT treatment from day -1 to day +2 post-immunization significantly reduced splenic size and the absolute number of Tag-specific T(CD8) on day 6 post-immunization. In vivo killing activity was also reduced. However, by day 10 post-immunization, the peak of the immune response, the absolute number of Tag-specific T(CD8) and their in vivo killing of epitope I or epitope IV-expressing target cells had recovered in CORT treated mice. Adoptive transfer of transgenic T cells post-CORT removal demonstrated that CORT decreased the ability of the endogenous antigen-presenting cells to induce proliferation of the exogenous transgenic T cells. Combined, these studies have implications about the timing of clinical steroid treatment relative to immunization or adoptive transfer for cancer immunotherapy.