Peripheral blood cytotoxic gammadelta 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.
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.NKR, 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 gammadelta CTL are abnormally expanded in the peripheral blood of HIV-infected patients and that the Vdelta1 subset of gammadelta T cells is the main effector population responsible for this type of cytolysis. The present data suggest that gammadelta 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.
Sindhu
Sardar T A K
ST
Laboratory of Immunovirology, Department of Microbiology and Immunology, Ste. Justine Hospital Research Center and Hotel-Dieu Hospital, University of Montreal, Montreal, Quebec, Canada.
Ahmad
Rasheed
R
Morisset
Richard
R
Ahmad
Ali
A
Menezes
José
J
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D003602:Cytotoxicity, Immunologic; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load
D016692:Receptors, Antigen, T-Cell, gamma-delta