Role of B7.2-mediated costimulation in Tcell homeostasis

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The immune system is tightly controlled to acheive the defense against an array of foreign pathogens and to prevent immune-mediated damage to our own cells. Because of their role in regulating immune responses, there has been a considerable interest in the identification of receptors and their ligands that are expressed on lymphocytes and which are necessary to promote their activation, inactivation or elimination. One of the most important receptor-ligand pairs mediating the activation of lymphocytes is CD28 which is expressed on T lymphocytes and B7.2 which is found on cells specialized in the presentation of antigen. The receptor CTLA-4 also binds B7.2, but is a negative regulator of T lymphocyte functions. In order to gain a better understanding of the influence of B7.2 on immune responses, we inserted a gene in mice that allows permanent expression of this molecule. We found that alterations of B7.2 expression have profound and differential effects on the homeostasis and differentiation of the two subsets of T lymphocytes, indicating a substantial role for these molecules in regulating the development and homeostasis of T lymphocytes. I propose a detailed study which should allow the elucidation of the mechanisms by which these molecules control this important function of the immune system. These studies have important implications for understanding the regulation of T lymphocytes in vivo.