Background: CD38 is an antigen whose expression on CD8+ T cells is a marker of lymphocyte activation and shows elevated expression during HIV-1 infection. Recent work has shown that intensity of CD38 on CD8+ cells is an important predictor of disease progression.
Objective: The aim of this study was to estimate the number of CD38 Abs bound per CD8+ T cell (CD38-ABC) and to examine the relationships among CD38 expression and viral load by using quantitative three-color flow cytometry (QFCM). (MoAbs :BD)
Design: The study carried out in 51 treatment experienced HIV-1 patients (pts). Seventeen pts with HIV RNA (vRNA)<50c/ml, 17 pts with 50c/ml<vRNA<1000c/ml and 17 pts with RNA>1000c/ml.
Results: 1) HIV-1(+) pts with VL>1000c/ml had significantly increased expression of CD38 ABC when compared among pts with 50c/ml<VL<1000c/ml and VL<50c/ml (A NOVA : p=0.001 between three groups). 2) CD38 ABC exhibited. a) Two fold elevation on CD8+DR+ cells (9232±3389 ABC) in comparison with CD8+DR- cells (4741±750 ABC) in patients with VL>1000c/ml (p=0.05). b) Three fold elevation on CD8+DR+ cells in pts with VL>1000c/ml in comparison with CD8+DR+ cells (3065±384 ABC) in pts with VL<50c/ml. 3) In HIV-1(+) pts with VL>1000c/ml there was a statistically significant increase at CD8+DR+ cells expressing more than 12000 CD38 molecules per CD8+ T cell (24.0±4.3%) compared with
(5.5±1.1) in pts with VL<50c/ml (p=0.001). There was also strongly positive correlation between VL and CD8+DR+ cells that express more than 12000 CD38 ABC (r=0.537, p=0.000). 4) Viral load was found to be in strong positive correlation with CD38 ABCs on both CD8 (r=0.348, p=0.028), CD8+DR+ (r=0.403, p=0.01) and CD8+DR- (r=0.333, p=0.036) subpopulations.
Conclusions: The increase of viral load leads to strong activation of circulating CD8 lymphocytes resulting in increased CD38 ABC expression. The high correlation between viral load and CD38 ABC on CD8 as well as their subpopulations and the high proportion of CD8+ cells and their subpopulations that express more than 12000 CD38 molecules per cell, shows that CD8 T cell activation determined by viral load reflect a separate pathogenic component of HIV-1 disease.
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