Title

Interleukin-2 and the regulation of CD8 T cell responses

Date of Completion

January 2003

Keywords

Health Sciences, Immunology

Degree

Ph.D.

Abstract

Interleukin-2 is a cytokine produced primarily by activated T cells and in vitro studies have led to the belief that IL-2 is crucial for initiation of cell cycle of activated T cells. Using an adoptive transfer system with IL-2- or IL-2R-deficient TCR transgenic CD8 T cells, we examined the in vivo role for IL-2 in CD8 T cell responses. Our results demonstrated that CD8 T cells produced IL-2 immediately following activation and prior to cell division. Nonetheless, the initial division of antigen-specific CD8 T cells following priming was IL-2 independent, regardless of the context in which antigen was presented. We also observed that early on in the response, autocrine IL-2 negatively regulated the overall magnitude of the CD8 T cell response in non-lymphoid tissues. In contrast, the latter stage of the proliferative phase was dependent upon IL-2, particularly in the non-lymphoid sites. Thus, activated CD8 T cells initiate proliferation in an IL-2 independent manner but reach a critical juncture where the requirement for IL-2 as a growth factor gains prominence. ^