The specificity of the adaptive immune response and regulation of its effector functions are mediated by the T helper lymphocyte. The goals of Dr. Crow's laboratory are to elucidate the mechanisms through which T helper cells are activated, to characterize the regulation of the cell surface molecules that mediate T cell help, to investigate the role of T cell help in the induction of B cell activation and differentiation, and to study the mechanisms of downregulation of T helper cell activity. The focus of this research is the normal human immune system, as well as the autoimmunity characteristic of the prototypic systemic autoimmune disease, systemic lupus erythematosus (SLE).

Research projects ongoing in the laboratory include: 1) Induction of autoantigen-reactive T helper cells. The conditions that permit self-antigens to "break tolerance" and activate autoantigen-specific T helper cells are being defined. 2) Regulation and function of CD40 ligand. CD40 ligand is the key cell surface molecule that mediates the activation of target cells by T helper cells. The laboratory is investigating the essential regulatory elements in the human CD40L promoter, the functional consequences of an altered CD40L promoter in systemic autoimmunity, and the molecular basis of increased expression of CD40L in SLE. 3) The role of CD40 ligand in B cell activation and immunoglobulin class switching. The functional consequences of CD40 ligation are being determined in purified human B cell populations from normal subjects and patients with SLE. 4) Cytokine regulation of Fas-mediated apoptosis. The effects of IL-10 and interferon-alpha on Fas ligand expression and target cell apoptosis through the Fas pathway are being investigated.