HIV-mediated defects in immune regulation

The Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), sponsored a Workshop on HIV-Mediated Defects in Immune Regulation on September 29-30, 1993. Workshop participants included investigators in basic research of immune regulation, animal models of HIV disease, HIV epidemiology, and HIV clinical research and treatment. The purpose of the workshop was to describe and evaluate biological mechanisms of HIV-mediated immune deficiency other than direct killing of infected CD4+ cells. The workshop focused on HIV-mediated dysfunction in signal transduction and in T cell development and maturation. Mechanisms by which HIV has been proposed to influence signal transduction include gp120 ligation to CD4, HIV superantigen(s), and HIV-mediated perturbations in signal pathway components (e.g., receptors, kinases, phosphatases, cytokines, and cyclins). As a result of signal dysfunction, cells may fail to respond to foreign antigens (anergy) or become predisposed to enter suicide pathways, otherwise known as programmed cell death or apoptosis. Programmed cell death is a normal immune regulatory mechanism that is activated to prevent anti-self responses and also to delete expanded but no longer needed cell populations. In the immune system, new cells are constantly produced from stem cells to replace those that die from age, pathological response, or programmed cell death. Dysfunction in these new cells may occur if HIV causes changes in the structural environment of the thymus and lymph nodes, or in cytokine signals.