Increased expression of CD40 ligand on systemic lupus erythematosus lymphocytes

The specificity of T cell help for B cell activation and differentiation is maintained by the brief expression on the T cell surface, following T cell receptor-mediated triggering, of CD40 ligand (CD40L). Interaction of T helper (T-h) cell CD40L with B cell CD40 induces B cell activation, cell surface expression of activation antigens, proliferation, and initiation of immunoglobulin isotype switch, We predicted that in patients with systemic lupus erythematosus (SLE), in whom T-h cell-dependent production of autoantibodies results in immune complex-mediated tissue damage, CD40L expression might be augmented, prolonged, or abnormally regulated, Baseline expression of CD40L was increased in some SLE patients studied, when compared with control subjects, While T-h cells from normal subjects (n = 14) and rheumatic disease control patients (n = 9) showed maximal expression of CD40L, after in vitro activation with phorbol myristate acetate (PMA) and ionomycin, at 6 h of culture with diminished levels observed at 24 and 48 h. T-h cells from SLE patients (n = 19) maintained high level cell surface expression of CD40L through 24 and 48 h of culture, The prolonged expression of CD40L was functionally significant, as 24 h-activated SLE T cells, when cocultured with target B cells, induced greater B cell surface CD80 (B7-1) expression than did 24 h-activated normal T cells. These results document impaired regulation of CD40L expression in SLE T cells and identify an important potential target for therapy in this systemic autoimmune disease.