The induction of lymphoproliferative responses to antigens or mitogens is dependent upon the release of Interleukin 2 (IL2) and the expression of receptors for this lymphokine (IL2R) on the surface of responding cells. A number of human diseases are associated with abnormalities in the production and function of IL2 including AIDS, autoimmune disorders and primary immunodeficiencies and aging. We will explore the interactions of IL2, IL2 receptors and lymphocyte proliferation with thymic hormones (TH), to determine the mechanisms involved in the regulation of the IL2 system and the immunomodulatory activities of TH. Using the synthetic polypeptide thymosin alpha 1 and other thymic hormones, we will analyze the mechanisms involved in the enhancement of IL2 production, by determining the kinetics of the response and the regulation of the IL2 gene expression. In addition, using a limiting dilution analysis, we will define the effects of TH on the frequency of the cells that produce IL2, and on the amount of IL2 produced by each cell during mitogen stimulation. We will characterize the mechanisms involved in the regulation of IL2R expression by TH, by radiobinding assays, flow cytometry and IL2 induced proliferation. We will determine the role of the enhancement of IL2 production on the induction of increased IL2R expression, and the effects of TH on the levels of cytoplasmic IL2R mRNA, by hybridization to a specific cDNA probe. We will explore the effects of TH on the IL2induced transferrin receptor expression. We will determine the phenotype of the lymphocyte subpopulation(s) and the role of accessory cells during TH modulation of IL2 production and IL2R expression. Using synthetic thymic hormone polypeptides, we will attempt to identify whether other molecules in addition to thymosin alpha 1 can mediate the enhancement of IL2R expression.
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