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 gammadeltaTCR-bearing CTL in blood and their MHC-unrestricted killing activity was blocked significantly (P < 0.01) by gammadeltaTCR-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 gammadeltaCTL in the peripheral blood.
Sindhu
S T A K
ST
Laboratory of Immunovirology, St Justine Hospital, Montreal, Canada.
Ahmad
R
R
Blagdon
M
M
Ahmad
A
A
Toma
E
E
Morisset
R
R
Menezes
J
J
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006461:Hemolysis; D006801:Humans; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D018709:Statistics, Nonparametric; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load
D015415:Biomarkers