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 host 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 mechanisms that contribute to HIV-associated lymphocyte apoptosis include chronic immunologic activation; gp120/160 ligation of the CD4 receptor; enhanced production of cytotoxic ligands or viral proteins by monocytes, macrophages, B cells, and CD8 T cells from HIV-infected patients that kill uninfected CD4 T cells; and direct infection of target cells by HIV, resulting in apoptosis. Although HIV infection results in T-cell apoptosis, under some circumstances HIV infection of resting T cells or macrophages does not result in apoptosis; this may be a critical step in the development of viral reservoirs. Recent therapies for HIV effectively reduce lymphoid and peripheral T-cell apoptosis, reduce viral replication, and enhance cellular immune competence; 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.
Badley
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Ottawa Hospital Research Institute and the Division of Infectious Diseases, Ottawa Hospital, Ottawa, Ontario, Canada. abadley@ottawahospital.on.ca
Pilon
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AA
Landay
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A
Lynch
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DH
D017209:Apoptosis; D001402:B-Lymphocytes / Q000473:pathology / Q000502:physiology / Q000821:virology; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008214:Lymphocytes / Q000473:pathology / Q000502:physiology* / Q000821:virology*; D008264:Macrophages / Q000473:pathology / Q000502:physiology / Q000821:virology; D013601:T-Lymphocytes / Q000473:pathology / Q000502:physiology / Q000821:virology