Title

The role of beta2 integrins in host responses to bacterial infection and T cell development

Date of Completion

January 2012

Keywords

Biology, Cell|Biology, Microbiology|Health Sciences, Immunology

Degree

Ph.D.

Abstract

Integrins are heterodimeric adhesion molecules that play an important role in cell-to-cell, as well as cell-to-endothelium interactions in the immune system. The members of the (β2 integrin family all share a common β2 chain but are complexed to distinct α chains CD11a, CD11b, CD11c and CD11d. A clear function of these adhesion molecules in CD8 T cell activation in vivo has not been well characterized. Therefore, to determine the role of (β2 integrins in vivo, we utilized mice deficient in specific (β2 integrins and characterized CD8 T cell responses after bacterial infection. We discovered that unlike CD11b and CD11c, the absence of CD11a expression severely blunted CD8 T cell primary responses and altered effector differentiation. Our data demonstrated that CD11a expression on naïve CD8 T cells was required for optimal activation and proliferation in response to immune insult. Interestingly, CD11a expression was not similarly required by memory CD8 T cells in response to secondary bacterial infection. Moreover, we have also identified a novel role of CD11a in early development of T cells. Our data demonstrated that in competitive reconstitution assays, CD11a deficient T cells failed to develop in the periphery of host mice. We have shown that this defect was a result of depletion of the common lymphoid progenitors within the bone marrow in the absence of CD11a. Thus, CD11a expression can influence the efficiency of CD8 T cell responses by regulating multiple stages of T cell life. ^