This is a request for a ADAMHA Research Scientist Award (RSA). This RSA will allow me the opportunity to develop and test models related to the modulation of T-cell function by catecholamines. The importance of this form of psychoneuroimmunology (PNI) can be found in the observation that catecholamines participate in the stress response and thus have the potential to be immunomodulatory. This gives rise to the possibility that catecholamines may modulate T-cell function in patients with AIDS related dementia. The overall objective of the research proposal in this grant is to elucidate the cellular, biochemical and molecular mechanisms involved in the regulation of T-cell activation and subsequent function as a consequence of the stimulation of the beta adrenergic receptor (BAR) on these cells. These studies will examine second messenger amplification or modulation in human T-cells stimulated through the BAR and/or the T-cell receptor complex (TCR). Experiments are proposed to determine at the biochemical level the mechanisms involved in the synergistic rise in cAMP in T-cells stimulated through the BAR and TCR. As a consequence of this dual stimulation of T-cells, experiments will be done to investigate perturbations in early transmembrane events elicited through stimulation of the TCR. The role of the activation of PKA in this process will be investigated. Finally a series of immunologic experiments are proposed to define the effects of catecholamines on T-cell proliferation induced by specific and non-specific stimuli.
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