Title

Parameters influencing memory differentiation of T cells

Date of Completion

January 2009

Keywords

Health Sciences, Immunology

Degree

Ph.D.

Abstract

Immunological memory is a cardinal feature of the adaptive immune response and the generation of long-lived memory T cells is critical in the development of effective vaccines. However, the precise mechanisms by which an activated T cell differentiates to a memory cell remain nebulous. To investigate the requirements necessary for the development of memory CD4 T cells we used an adoptive transfer system and an in vivo model of infection. We demonstrated that the initial precursor frequency of cells entering the immune response was inversely related to the function and survival of the cells. We formally demonstrated that this defect was due to competition by regulating the amount of antigen available at the time of T cell priming. We also examined the requirements for the duration of antigen availability to generate a productive immune response. We demonstrated that both CD4 and CD8 T cells required prolonged antigenic stimulation for optimal expansion to occur. However, shorter durations of antigen availability were sufficient for the generation of memory T cells. Thus, antigen availability during the early phases of the immune response is important in regulating programmed T cell expansion and differentiation. ^