Title

Dynamics of anti-microbial CD8 T cell responses

Date of Completion

January 2002

Keywords

Biology, Microbiology|Health Sciences, Immunology

Degree

Ph.D.

Abstract

CD8 T lymphocytes are crucial for the elimination of many intracellular pathogens. Many pathogens infect a broad range of host tissues, rarely limited to that of the immune system. Yet, much of our understanding of T cell responses comes from analyses of lymphoid tissue. Thus, significant questions remain regarding the dynamics of T cell responses within non-lymphoid tissues, sites where memory cells may provide the most effective protection. Outstanding issues concern (1) the migration patterns of primary cytotoxic T lymphocytes (CTL), (2) the migration patterns of memory CD8 T cells, and (3) the effector function of peripheral memory CD8 T cells. It was shown, in response to viral or bacterial infection, antigen-specific CD8 T cells marginated into non-lymphoid tissues and remained present as long-lived memory cells. Furthermore, T cell activation endowed CD8 T cells with the ability to traffic into all non-lymphoid tissues, irrespective of the site of infection or priming. Phenotypic differences were notable between memory populations in lymphoid versus non-lymphoid tissues and between memory cells in different organs. Strikingly, CD8 memory T cells isolated from peripheral tissues were highly lytic directly ex vivo, in contrast to their splenic counterparts. These results point to the existence of a population of extra-lymphoid memory T cells poised to immediately respond to an infection. These results will have an important bearing on controversies surrounding the contribution of CD8 T cells to protective immunity, will support or question vaccine efforts that specifically target CTL responses, and have been previously overlooked because most studies focus solely on lymphoid T cells. ^