Timing of corticosterone treatment and its effects on the CD8+ T cell response to cell-associated antigen (87.18)

Abstract

Abstract Exposure of T cells to glucocorticoids alters their normal program of activation and expansion. In vitro work, often with the synthetic analog, dexamethasone, demonstrated a direct effect of glucocorticoids on T cell proliferation after antigen exposure. In vivo studies have also often utilized dexamethasone. In the current study we evaluated the effect of in vivo administration of the natural glucocorticoid, corticosterone (CORT), on the CD8+ T cell response to SV40 large T antigen (Tag)-expressing cells. C57BL/6 mice respond with a hierarchical CD8+ T cell response to Tag in which epitope IV (amino acids 404-411) is dominant and epitope I (206-215) is subdominant. Exposure to CORT over the course of the immune response to Tag, decreased the number of splenocytes by ~83%. The CD8+ T cell response to epitope I and epitope IV was almost completely abolished during the primary response. Tag-specific memory T cells were also severely affected by CORT treatment. Even when CORT was provided after cross-priming had occurred, the primary T cell response to Tag was still largely inhibited. The ratio of epitope I:epitope IV-specific CD8+ T cells was slightly increased in CORT-treated mice, suggesting that epitope IV-specific T cells may be more susceptible to CORT. Further studies will provide insight regarding when CORT exposure is most detrimental to CD8+ T cell responses that rely on both cross- and direct presentation to achieve maximal expansion.