Increased expression of CD40 on thymocytes and peripheral T cells in autoimmunity: A mechanism for acquiring changes in the peripheral T cell receptor repertoire

CD40, a cell surface molecule found on B lymphocytes and other antigen pres enting cells, can, when engaged by CD40 ligand (CD40L), induce gene rearran gements and isotype switching. We report here that CD40 is also expressed o n thymocytes and on up to 50% of peripheral T cells from autoimmune prone s trains of mice. In normal animals, CD40 is present on a small population of T cells and thymocytes. CD40 is expressed on most T cell hybridomas. We de monstrate that CD40 engagement on peripheral T cells, T cell hybridomas and thymocytes results in altered TCRV alpha expression. That induced expressi on of different Vee's results from the activity of the recombinase gene is implied by the observation that CD30 does not induce TCR changes in RAG kno ck-out mice. Total cell numbers remained unchanged between anti-CD40 treate d and untreated populations of thymocytes or T cells indicating that treatm ent does not induce cell proliferation or cell death. The data presented he re suggest a mechanism by which self reactive T cells accumulate peripheral ly and independently of selective processes of the thymus.