Virus load correlates inversely with the expression of cytotoxic T lymphocyte activation markers in HIV-1-infected/AIDS patients showing MHC-unrestricted CTL-mediated lysis

Cytotoxic T lymphocytes (CTL) are key players to suppress viral load (VL) but CTL responses become compromised with progression of HIV-infection/AIDS. Some progressors develop MHC-unrestricted CTL with anti-CD4 ⁺ cytocidal activity. Immune activation status of these CTL and its significance in disease progression are unknown. To determine the relationship between VL and T cell activation, a cross-sectional study was carried out using blood samples from 13 HIV-1-infected/AIDS patients at various stages of progression and seven age-matched seronegative controls. We examined expression of HLA-DR and CD38 activation markers on purified CTL. MHC-unrestricted killing by these CTL was also evaluated against uninfected, allogeneic CD4 ⁺ T cells as well as several human cell lines. The expression of activation markers correlated inversely (rs = - 0.91, P < 0.0001) with VL of the subjects. CTL effectors of these patients killed targets expressing or lacking CD4 ⁺ , independently of MHC class I recognition. Interestingly, the patients with higher VL showed an increased number of γδTCR-bearing CTL in blood and their MHC-unrestricted killing activity was blocked significantly (P < 0.01) by γδTCR-specific monoclonal antibody. CD3 ⁺ T counts of these patients were also consistently subnormal. Inverse correlation between VL and CD8 ⁺ T cell activation markers seems to be an indicator of CTL-associated immunopathogenesis in HIV patients with elevated γδCTL in the peripheral blood.