Effects of androgens on T and B lymphocyte development

The sexually dimorphic nature of normal immune responses and the remarkably higher incidence of autoimmune diseases its females have suggested a role for gonadal steroid hormones as modulators of immune system function. We ha ve investigated the effects of androgens on the development of lymphocytes in the thymus and bone marrow. Expression of the androgen receptor, the lig and-activated transcription factor that mediates hormone actions, has been documented in lymphoid and nonlymphoid cells of thymus and bone marrow, but not in mature peripheral lymphocytes. This expression pattern suggests tha t the major impact of androgens must be on the developmental maturation of T and B lymphocytes rather than on the mature effector cells. Recent experi ments have explored whether developing lymphoid precursors are the direct t argets of androgen action or whether supporting cells, such as thymic epith elial cells and bone marrow stromal cells, are required for the receptor-me diated effects of androgens on lymphoid cell development. Bone marrow trans plantation techniques using an androgen-resistant mouse strain permit the c reation of chimeric mice with androgen receptor-defective lymphoid or epith elial/stromal cellular compartments. Hormonal manipulation experiments in t hese chimeric animals have suggested that thymic epithelial cells and bone marrow stromal cells are mediators of androgenic effects an immature lympho cytes. The long-range goal of these studies is to understand the basis for the disproportionate occurrence of autoimmune diseases in females.