The molecular basis for T cell help in humoral immunity: CD40 and its ligand,gp39

Summary The identification of the gp39-CD40 as an essential ligand-receptor pair for TD humoral immunity offers new insights into the regulation of TD immune responses. It is apparent that alterations in the regulation of gp39 expression, either by mutations in the gp39 gene (HIM patients) or by other factors that influence expression (like cyclosporine), have an overwhelming effect on humoral immunity. Whether other arms of the immune response are targets of gp39 action is unknown at this time. However, the identification of CD40 as the receptor for gp39 provides clues as to other CD40-expressing cell types (folicular dendritic cells, thymic epithelial cells, etc.) that might be regulated by activated CD4⁺ T cells. The immunosuppressive effects of anti-gp39 on primary and secondary humoral immunity, as well as the beneficial therapeutic effects of anti-gp39 on the progression of autoimmune disease in animal models, suggest that this ligand-receptor pair is an ideal target for the therapeutic intervention.