The objectives of laboratory research project B in this proposal are to study selected aspects of monocyte-macrophage (MO) immunobiological function in individuals through the full spectrum of HIV infection from stage I-IV (AIDS). The design of the clinical section of this proposal is uniquely suited for early case finding in stage I which, heretofore, has not been studied well immunologically. Serial studies of selected monocyte-MO function will be performed over a period of up to 5 yr. The capacity of mononuclear cells from HIV-infected patients (stages I-IV) to produce interleukin I (IL1), a cytokine critical to augmentation of the immune response, will be studied. If deficient IL1 production is detected, the mechanism of this impairment will be analyzed and attempts made to reverse the defect by pharmacological or immunological means. Others studies will attempt to confirm reports of abnormal directed migration (chemotaxis) by PBM cells in stages III and IV of HIV disease, as well as searching for disordered chemotactic activity by PBM cells from patients in stages I and II. Sera from patients will be analyzed for the presence of a factor(s) that acts directly on cells to impair migration, or alternatively, that inactivates chemoattractants such as C5a. The effects of HIV glycoproteins on PBM cell migration and of HIV infection of normal PBM cells will be studied. Since there is evidence that the adherence properties of PBM cells from HIV-infected patients may be abnormal, detailed studies of the adherence-promoting surface glycoproteins (CR3/LFA-1/p150,95) will be studied on the cells and on cells from normal controls. The relative numbers of and functional activity of CR3 will be studied in conjunction with activity levels of the low avidity Fc receptor and the mannosyl-fucosyl receptor. The capacity of monocytes from HIV-infected and normal donors to increase receptor expression during maturation to monocytes in vitro will be analyzed.
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