Browsing by Subject "Homeostatic proliferation"
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Item Derivation, maintenance, and functions of virtual memory cells.(2011-09) Akue, Adovi DodjiMemory phenotype CD8+ T cells are typically thought to have undergone an immune response to foreign antigen and to have differentiated from antigen-specific precursors in the naïve pool. However, using a peptide-MHC I tetramer enrichment technique, we identified foreign antigen-specific memory-phenotype CD8+ T cells in unimmunized mice. These cells (termed "virtual memory" T or VM cells) were observed in mice maintained in both specific-pathogen- and germ-free (SPF and GF respectively) housing. This thesis focuses on the relationship between VM cells and "conventional" memory cells: memory cells arising from homeostatic proliferation (HP), and innate-like memory CD8+ T cells such as IL-4 bystander memory CD8+ T cells. Our data indicate physiological HP and IL-4-driven bystander processes are the main mechanisms that drive the generation of VM cells and not the exposure to foreign antigens. VM cells arise in the periphery during the neonatal period and are maintained long term. We also show that VM cells respond in vitro to innate cytokines (similar to conventional memory CD8+ T cells) and they outcompete antigen-specific naive CD8+ T cells in in vivo responses. Overall our observations suggest that VM cells arise out of normal homeostatic and IL-4-driven bystander processes in unimmunized SPF and GF mice, and express at least some memory-like capabilities.Item Regulation of cluster of differentiation eight positive (CD8+) T cell homeostatic proliferation.(2010-05) Johnson, Lisa Danae SchultzThe 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.