Ontogeny of Immunity in Frogs/Thyroid Hormone Effects

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Previous studies of the immune responses of tadpoles and adult South African clawed frogs, Xenopus laevis, have shown that tadpole responses are generally poorer, indicative of an immature immune system. Because immune responses improve after metamorphosis, and this improvement appears to be thyroxine dependent, it is postulated that the hormonal changes at metamorphosis transform the larval immune system to an adult- type system. Specifically, it is proposed that a population of larval lymphocytes is destroyed at metamorphosis and is replaced following a new wave of hematopoiesis by another population that will function in the adult. The studies proposed here are designed to examine further the immunological deficits that result from low thyroid hormone concentrations during development and metamorphosis, to establish more clearly whether a distinct larval lymphocyte population exists, and to examine the effects of altered thyroid hormone concentrations during metamorphosis on the decline of the putative larval population and emergence of the adult population. Direct effects of thyroid and corticosteroid hormones on the viability and function of cultured lymphocytes from premetamorphic tadpoles, metamorphosing tadpoles, and adult frogs will also be studied. Finally, a study of the expression of Class I MHC antigens in precociously metamorphosis frogs will test the hypothesis that altered skin allograft rejection responses in these frogs is due to premature expansion of the adult lymphocyte population prior to expression of Class I antigens. Because tadpoles develop as free-living organisms they need a functional immune system to protect them from environmental pathogens. The larval immune system must change during metamorphosis to accomodate new adult-specific antigens, or these antigens would be recognized as foreign and the metamorphosing tadpole would begin to destroy itself. Understanding how the immune system changes at metamorphosis and the role of various metamorphosis-related hormones in these changes should give us greater insight into the process by which self-recognition and immunological tolerance to self develop.