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
University of Minnesota Ph.D. dissertation. May 2010. Major:Microbiology, Immunology and Cancer Biology. Advisor: Stephen C. Jameson, Ph.D. 1 computer file (PDF); vii, 111 pages.
Johnson, Lisa Danae Schultz.
Regulation of cluster of differentiation eight positive (CD8+) T cell homeostatic proliferation..
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