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Journal of Virology, February 2003, p. 1848-1855, Vol. 77, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.3.1848-1855.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Peripheral Blood Cytotoxic T Lymphocytes from Patients with Human Immunodeficiency Virus Type 1 Infection and AIDS Lyse Uninfected CD4⁺ T Cells, and Their Cytocidal Potential Correlates with Viral Load

Laboratory of Immunovirology, Department of Microbiology and Immunology, Ste. Justine Hospital Research Center and Hotel-Dieu Hospital, University of Montreal, Montreal, Quebec, Canada

Received 8 August 2002/ Accepted 6 November 2002

Progression of human immunodeficiency virus type 1 (HIV-1) infection in humans is marked by declining CD4⁺-T-cell counts and increasing virus load (VL). Cytotoxic T lymphocytes (CTL) play an important role in the lysis of HIV-infected cells, especially during the early phase of asymptomatic infection. CTL responses in the later phase of disease progression may not be as effective since progressors with lower CD4⁺-T-cell counts have consistently higher VL despite having elevated CTL counts. We hypothesized that, apart from antiviral effects, some CTL might also contribute to AIDS pathogenesis by depleting CD4⁺ T cells and that this CTL activity may correlate with the VL in AIDS patients. Therefore, a cross-sectional study of 31 HIV-1-infected patients at various clinical stages was carried out. Purified CTL from these donors as well as HIV-seronegative controls were used as effectors against different human cell targets by using standard ⁵¹Cr release cytolytic assays. A direct correlation between VL and CTL-mediated, major histocompatibility complex (MHC)-unrestricted lysis of primary CD4⁺-T-cell, CEM.NK^R, and K562 targets was observed. CD4⁺-T-cell counts and duration of infection also correlated with MHC-unrestricted cytolytic activity. Our data clearly show that CTL are abnormally expanded in the peripheral blood of HIV-infected patients and that the V1 subset of T cells is the main effector population responsible for this type of cytolysis. The present data suggest that CTL can contribute to the depletion of bystander CD4⁺ T cells in HIV-infected patients as a parallel mechanism to HIV-associated immunopathogenesis and hence expedite AIDS progression.

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