Regulation of cluster of differentiation eight positive (CD8+) T cell homeostatic proliferation.

Abstract

The adaptive immune system provides protection against pathogens during a primary infection and generates a reservoir of memory cells that quickly and effectively responds to subsequent encounters with that pathogen for the lifetime of the organism. The goal of modern day vaccination is to generate such memory in the absence of primary infection. Infection or vaccination, however, is not the only method of providing immunological memory. The expansion of T cells in response to lymphopenia, termed homeostatic proliferation, generates memory CD8+ T cells in the absence of cognate antigen and costimulation. Factors such as self-peptide MHC interaction and common-γ chain cytokines are essential for this process. The extent of homeostatic proliferation can be modulated by cytokines that promote and inhibit homeostatic proliferation as well as the sensitivity of the T cell receptor (TCR) to self-peptide MHC. This thesis describes 1) the effect of transforming growth factor beta (TGF-β) on the generation of memory CD8+ T cells and 2) homeostatic proliferation of self- and tumor- specific CD8+ T cells. Collectively, this work provides insights for the design of T cell based vaccines, particularly tumor immunotherapy.