T-CELL ACTIVATION AND DISEASE SEVERITY IN HIV-INFECTION

In vitro studies have indicated that T lymphocyte activation may be of importance in the pathogenesis of HIV infection. In order to define t he role of immune activation in vivo, we assessed the expression of th e T cell activation markers HLA-DR and CD25 by flow cytometry in perip heral blood in relation to disease severity and the surrogate markers CD4 and beta2-microglobulin in 157 patients with HIV infection and 53 healthy seronegative blood donors. Percentage levels of CD3+HLA-DR+ T lymphocytes were significantly higher (P<0.0001) and percentage levels of CD3+CD25+ T lymphocytes significantly lower (P<0.0001) in all HIV patients compared with controls. A significant correlation was observ ed between increasing percentage levels of CD3+HLA-DR+ T lymphocytes a nd both declining CD4 counts (r=0.52; P<0.001) and increasing beta2-mi croglobulin levels (r=0.56; P<0.001). Percentage levels of CD4+HLA-DR and CD4+CD25+ lymphocytes were significantly higher in all HIV+ patie nts compared with controls (P<0.001). Levels of activated (HLA-DR+ and CD25+) CD4+ lymphocytes showed a significant step-wise linear increas e with increasing disease severity (P<0.001). High levels of CD3+HLA-D R+ T lymphocytes were found in a greater proportion (81.8%) of asympto matic HIV+ patients (Centres for Disease Control (CDC) group II) than low CD4 counts (51.5%) (P<0.001). Compared with controls, HIV+ patient s had higher percentage levels of CD8+HLA-DR+ lymphocytes (P<0.001), b ut similar levels of CD8+CD25+ lymphocytes. These results indicate tha t T cell activation is not only a consistent but also an early feature in HIV infection. Monitoring levels of activated T cells and their su bsets is of value in assessing progression of HIV-related disease.