FUNCTIONAL CONSEQUENCES OF DYSREGULATED B7-1 (CD80) AND B7-2 (CD86) EXPRESSION IN B-LYMPHOCYTE OR T-LYMPHOCYTE OF TRANSGENIC MICE

T cell activation and tolerance are regulated by interactions between CD28 or CTLA-4 on T cells and B7 costimulatory molecules on APCs. We h ave generated transgenic mouse strains that constitutively express B7- 1 (CD80) at high levels on B cells or T cells or express B7-2 (CD86) o n T lymphocytes to examine the consequences of dysregulated B7 express ion on T cell responses. The transgene-derived B7 molecules are functi onal, because B7-1 transgenic B cells are more efficient APCs than are wild-type B cells, and the activation of B7 transgenic T cells is les s dependent on exogenous costimulation than that of wild-type T cells. In vivo, constitutive expression of B7 molecules leads to the elimina tion of immature B cells. The expression of B7 molecules on thymocytes results in the down-regulation of CD28 expression. However, B7 transg enic mice have normal numbers of mature lymphocytes and mount normal T cell responses following immunization with protein Ag. Neither anergy induction nor superantigen-mediated deletion of T cells is altered by the dysregulated expression of B7-1 or B7-2 on B or T lymphocytes in these transgenic strains. Therefore, functionally significant levels o f B7 expressed constitutively on mature lymphocytes are not, by themse lves, sufficient to abrogate T cell tolerance or induce autoimmune dis ease.