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HIV-specific CD8+ T cells: serial killers condemned to die?
Journal article   Peer reviewed

HIV-specific CD8+ T cells: serial killers condemned to die?

Constantinos Petrovas, Yvonne M Mueller and Peter D Katsikis
Current HIV research, v 2(2), pp 153-162
Apr 2004
PMID: 15078179

Abstract

Apoptosis CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - physiology fas Receptor - physiology Gene Products, nef - physiology HIV - immunology HIV Infections - immunology Humans nef Gene Products, Human Immunodeficiency Virus Signal Transduction T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Cytotoxic - physiology Viral Proteins - physiology
An increasing body of evidence supports a key role for cytotoxic CD8+ T cells (CTL) in controlling HIV infection. Although a vigorous HIV-specific CD8+ T cell response is raised during the primary infection, these cells ultimately fail to control virus and prevent disease progression. The failure of CTL to control HIV infection has been attributed to a number of strategies HIV employs to evade the immune system. Recently, intrinsic defects in the CTL themselves have been proposed to contribute to the failure of CTL to control HIV. HIV-specific CD8+ T cells differ in their effector/memory phenotype from other virus-specific CD8+ T cells indicating that their differentiation status differs. This altered differentiation may affect effector functions as well as homing properties of these cells. Other studies have indicated that activation of HIV-specific CTL may be impaired and this contributes to their dysfunction. The effector function of these CTL may also be affected. There are conflicting reports about their ability to kill, whereas IFNgamma production does not appear to be impaired in these cells. In this review we focus on recent work indicating that apoptosis may be an important mechanism through which HIV evades the CTL response. In particular, HIV-specific CD8+ T cells are highly susceptible to CD95/Fas-induced apoptosis. This leads to the hypothesis that virus-specific cytotoxic T cells can be eliminated upon binding CD95L/FasL on HIV-infected cells. Understanding the intrinsic defects of CTL in HIV infection could lead to new therapeutic strategies and optimized vaccination protocols that enhance the HIV-specific cytotoxic response.

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Web of Science research areas
Immunology
Infectious Diseases
Virology
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