Mechanisms of HIV-associated lymphocyte apoptosis

Infection with the human immunodeficiency virus (HIV) is associated with a progressive decrease in CD4 T-cell number and a consequent impairment in ho st immune defenses. Analysis of T cells from patients infected with HIV, or of T cells infected in vitro with HIV, demonstrates a significant fraction of both infected and uninfected cells dying by apoptosis, The many mechani sms that contribute to HIV-associated lymphocyte apoptosis include chronic immunologic activation; gp120/160 ligation of the CD4 receptor; enhanced pr oduction of cytotoxic ligands or viral proteins by monocytes, macrophages, B cells, and CD8 T cells from HIV-infected patients that kill uninfected CD 4 T cells; and direct infection of target cells by HIV, resulting in apopto sis, Although HIV infection results in T-cell apoptosis, under some circums tances HIV infection of resting T cells or macrophages does not result in a poptosis; this may be a critical step in the development of viral reservoir s, Recent therapies for HIV effectively reduce lymphoid and peripheral T-ce ll apoptosis, reduce viral replication, and enhance cellular immune compete nce; however, they do not alter viral reservoirs. Further understanding the regulation of apoptosis in HIV disease is required to develop novel immune -based therapies aimed at modifying HIV-induced apoptosis to the benefit of patients infected with HIV, (C) 2000 by The American Society of Hematology .