Abstract
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.
Original language | English |
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Pages (from-to) | 120-127 |
Number of pages | 8 |
Journal | Clinical and Experimental Immunology |
Volume | 132 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Apr 2003 |
Keywords
- AIDS-pathogenesis
- CTL
- HIV load
- Immune activation markers
- MHC-unrestricted