INVOLVEMENT OF GLUCOCORTICOIDS IN THE REORGANIZATION OF THE AMPHIBIANIMMUNE-SYSTEM AT METAMORPHOSIS

In recent years, integrative animal biologists and behavioral scientis ts have begun to understand the complex interactions between the immun e system and the neuroendocrine system. Amphibian metamorphosis offers a unique opportunity to study dramatic hormone-driven changes in the immune system in a compressed time frame. In the South African clawed frog, Xenopus laevis, the larval pattern of immunity is distinct from that of the adult, and metamorphosis marks the transition from one pat tern to the other. Climax of metamorphosis is characterized by signifi cant elevations in thyroid hormones, glucocorticoid hormones, and the pituitary hormones, prolactin and growth hormone. Previously, we and o thers have shown that elevated levels of unbound glucocorticoid hormon es found at climax of metamorphosis are associated with a natural decl ine in lymphocyte numbers, lymphocyte viability, and mitogen-induced p roliferation. Here we present evidence that the mechanism for loss of lymphocytes at metamorphosis is glucocorticoid-induced apoptosis. Inhi bition of lymphocyte function and loss of lymphocytes in the thymus an d spleen are reversible by in vitro or in vivo treatment with the gluc ocorticoid receptor antagonist, RU486, whereas the mineralocorticoid r eceptor antagonist, RU26752, is poorly effective. These observations s upport the hypothesis that loss of larval lymphocytes and changes in l ymphocyte function are due to elevated concentrations of glucocorticoi ds that remove unnecessary lymphocytes to allow for development of imm unological tolerance to the new adult-specific antigens that appear as a result of metamorphosis.