2007-08-012024-05-16https://scholars.lib.ntu.edu.tw/handle/123456789/669770The immune system evolves sophisticated strategies to regulate immune responses. To induce an optimal activation, both CD4+ and CD8+ T cells require both an antigen-specific and costimulatory signals to proliferate and differentiate into effector cells. It has been reported in murine and human that the magnitude of CD8+ T cell response is greater than that of CD4+ T cells. However, the model of how T cells are activated has been examined CD4+ T cells. The preliminary results from my laboratory showed that CD8+ T cell activation is less dependent on CD28 costimulatory signal to reach proliferation potential. The goal of this proposal is to better understand the mechanisms that regulate CD8+ T cell activation. Establishment of in vitro activation of CD4+ and CD8+ T cells allows us to study the mechanisms that govern activation kinetics of CD8+ T cells. The aims of the study are (1) to investigate whether threshold of antigenic stimulation, ability to survive or susceptibility to cell death determines the activation kinetics of CD8+ T cells; (2) to determine whether less requirement for CD28 costimulation in CD8+ T cells rests on formation of a distinct pattern of immunological synapse; (3) to investigate the role of CD28 in CD8+ T cell activation in response to high- and low-dose antigens in vivo. My intent in this study is to investigate the mechanisms that determine the activation kinetics of CD8+ T cells and to indicate how these can be integrated into a more complete description of the T cell homeostasis. Such approaches will also be of value in taking us one step closer to augment CD8+ T cell responses for treating individuals with viral infection.