The long-term objective is to examine interactions betwen activated phagocytes and human lymphocytes. These studies are based on the premise that in situations of chronic inflammation, activated phagocytes releasse mediators such as certain prostaglandins and reactive oxygen species and thereby influence the subtype distribution and function of nearby lymphocytes. Our previous studies clearly showed that oxidants such as hydrogen peroxide (H2O2) when released from activated blood phagocytes inhibit in vitro T cell rosette formation, T cell proliferation, and mononuclear cell production of immunoglobulin. Preliminary data strongly indicate that T cells are not equally sensitive to physiological amounts of H2O2. For T cell-sheep erythrocyte rosette formation, there exists discrete peroxide sensitive and resistant T cell subpopulations with markedly different T cell subset distributions and proliferative functions. Oxidants other than H2O2, such as hypochlorous acid and N-chloroamines also inhibit T cell-rosette formation in non-lethal amounts. The present studies will examine in detail the effects of three phagocyte-released oxidants, H2O2, hypochlorous acid and N-chlorotauramine, on several important interrelated lymphocyte functions. Oxidants will be either added directly to lymphocytes or generated in vitro with activated phagocytes in the presence of selective oxygen radical scavengers. Specific oxidant effects on T cell rosette formation, T cell subset distribution, T cell subset and B cell proliferation, lymphokine production and response, and T cell subset regulation of B cell immunoglobulin production will be examined. T cells highly resistant to different oxidants will be developed through multiple exposure of activated lymphocytes to low level oxidants. Monoclonal antibodies will be produced against lymphocytes particularly sensitive or resistant to different oxidants for use as markers and reagents for cell separation in a more refined in vitro analysis and for in vivo detection purposes at chronic inflammatory sites. Data gathered from these studies should provide important insights as to how inflammatory mediators can alter in vitro immune reactivity and may provide important probes for further investigations of phagocyte-lymphocyte interaction in vivo.
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