83. Analysis of the effects of short-term corticosterone treatment on the CD8+ T cell response to a well-defined oncoprotein

Abstract

The CD8+ T cell-mediated immune response to the Simian Virus 40 oncoprotein, large tumor antigen (Tag), is hierarchical in C57BL/6 mice. Epitope IV, an H-2Kb-restricted epitope, is immunodominant while epitope I, an H-2Db-restricted epitope is subdominant. Exposure of mice to the immunosuppressive glucocorticoid, corticosterone (CORT) over the course of the primary immune response prevents expansion and detection of Tag-specific CD8+ T cells. Short-term CORT treatment from day −1 to day +2 (72 h) post-immunization with cells expressing Tag significantly reduced splenic size and the absolute number of Tag-specific CD8+ T cells present on day 6 post-immunization. In vivo killing of epitope I or epitope IV-expressing target cells was also reduced in a hierarchical manner on day 6 post-immunization. By day 10 post-immunization, the typical peak of the immune response to Tag, in vivo killing of epitope I or epitope IV-expressing target cells had recovered despite the sustained decrease in the absolute numbers of Tag-specific CD8+ T cells. This suggests that relatively few Tag-specific CD8+ T cells are necessary for cytotoxicity of target cells. Ongoing studies are isolating the effects of CORT on the antigen presenting dendritic cells using transgenic T cell adoptive transfer strategies. These studies have implications about the timing of clinical steroid treatment relative to immunization or adoptive transfer for cancer immunotherapy.