Memory CD8 T cell responses: Initiation, early kinetics, and secondary memory generation.

摘要

Antigen (Ag)-specific memory CD8 T cells confer protection against intracellular pathogens in vivo. Their increased protective capacity relative to their naive precursors is due to many factors, including an increased frequency in the host and a more rapid elaboration of cytokines and cytotoxic molecules. Generation of vaccination protocols that induce memory CD8 T cell formation has high potential in terms of the rational design of vaccines, especially in cases in which humoral immunity is not sufficient to protect against infection. Examinations of memory CD8 T cell generation, factors required for memory CD8 T cell responses, and the behavior of memory CD8 T cells in the context of infection may be informative in terms of the induction of more effective defenses against pathogenic infection.;My studies of CD8 T cells examine the requirements for the induction of a memory CD8 T cell response to stimulation with Ag, early events in the memory CD8 T cell response to infection, and the ensuing state of CD8 T cells after memory CD8 T cells have responded to infection. Specifically, my studies indicate (i) that secondary reponses by memory CD8 T cells to Ag does not require, and may be inhibited by, hostderived peptides presented in the context of MHC Class I, (ii) memory CD8 T cells undergo a process called T cell conditioning early after infection, and (iii) memory CD8 T cells generated after multiple infections are functionally distinct from memory CD8 T cells generated after a single infection. In total, these studies extend our knowledge of regulation of the memory CD8 T cell response, better define early events in the memory CD8 T cell response, and acknowledge that the function of memory CD8 T cells is affected by the number of antigenic experiences.