The acquired immunodeficiency syndrome (AIDS) is defined by the presence of opportunistic infections or tumors that do not occur in persons with normal immune function. Monocytes and macrophages that have been """"""""activated"""""""" form part of the host defense against infection and neoplasia. It has been proposed that any putative monocyte/macrophage defect simply reflects the absence of activating signals from CD4+ T cells that are depleted in AIDS. One such signal is interferon-gamma which activates macrophages for certain defense functions. T cells also induce monocytes and macrophages to (1) develop procoagulant activity, (2) release interleukin-1 and its inhibitor, (3) release tumor necrosis factor, and (4) express antimycobacterial activity. Immunolgically stimulated T cells induce these macrophage functions by means of lymphokines known to be distinct from interferon-gamma. I propose to examine these lymphokine systems in AIDS and ARC. Using blood from human immunodeficiency virus (HIV)-infected individuals, the ability of T cells to induce each of these four macrophage functions will be examined and compared to normal controls. Furthermore, since macrophages may be infected with HIV both in vivo and in vitro, I propose to study the ability of HIV to directly induce a primary monocyte/macrophage defect for each of these four functions independent of the effects of infection of T cells. Finally, the ability of lymphokines to affect the course of HIV production in macrophages will be examined. These studies should help clarify the immunological defects in AIDS and AIDS-related complex and may suggest strategies for their treatment.
Showing the most recent 10 out of 16 publications
