AGE RELATED EFFECTS ON T LYMPHOCYTE ADHESION

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Aging is accompanied by a progressive decrease in immune function, which affects both the humoral and cellular arms of the immune system. As a consequence, the elderly population becomes particularly susceptible to potentially life-threatening infections and cancers. Identifying key age-associated changes in the normal functioning of cells of the immune system thus becomes an important step in arresting or reversing the overall decline in the immune response. The initial interaction between a T lymphocyte and an antigen-presenting cell (APC) is a pivotal process in mounting an immune response. Antigen in the form of peptide/class Il MHC complexes is recognized by the clonotypic T cell receptor (TCR), in conjunction with the CD4 coreceptor. In addition, several non- antigen-specific or 'accessory' T cell molecules bind to ligands expressed on the APC, and thus facilitate adhesion between the two cell types. Over the last several years, the avidity of many T cell accessory molecule interactions has been shown to be acutely regulated by TCR engagement. Thus, once antigen has been recognized by the TCR, the strength of the accessory molecule interactions are rapidly increased, and as a direct consequence the accessory molecule participates in cosignaling for T cell activation. In the present application, we propose to examine age-related changes in TCR-upregulated adhesion and cosignaling by the T cell integrins LFA-1 (CDlla/CD18), VLA-4 (CD49d/CD29), VLA-5 (CD49e/CD29) and the vitronectin receptor (CD51 /CD61). Each of these integrins play important roles in the function of mature T cells from young animals; the results obtained will therefore provide valuable information on how aging influences the initial interaction T cells and their APC.