Title

Interleukin 15: New isoforms, dendritic cell biology and CD8+ T cell response

Date of Completion

January 2006

Keywords

Health Sciences, Immunology

Degree

Ph.D.

Abstract

This body of work has investigated three aspects of interleukin 15 biology. First, two new IL-15 mRNA isoforms generated by different alternative splicing events were identified preferentially from mouse intestinal epithelium. These IL-15 mRNA isoforms encoded in-frame truncated IL-15 protein variants. Functional analysis of the recombinant IL-15 isoform proteins suggested possible regulatory functions. Secondly, the effect of IL-15 on dendritic cell biology has been investigated in vitro and in vivo. In the absence of IL-15, DCs mature and are activated normally, and are competent to directly prime both naive and memory CD8+ T cells. However, IL-15 expression by DCs is required for their optimal cross priming of CD8 + T cells in vivo. In the last part of this thesis, the regulation of the CD8+ T cell response by IL-15 has also been studied using IL-15 deficient mice following acute viral infection. IL-15 was involved in the regulation of the CD8+ T cell response late in the expansion phase which, in conjunction with the dynamic expression of the IL-2 and IL-15 receptors may provide both cellular and molecular foundations to optimize immunotherapy following an acute infection.^