T cell activation and disease severity in HIV infection

Abstract

SUMMARY: In vitro studies have indicated that T lymphocyte activation may be of importance in the pathogenesis of HIV infection. In order to define the role of immune activation in vivo, we assessed the expression of the T cell activation markers HLA-DR and CD25 by flow cytometry in peripheral blood in relation to disease severity and the surrogate markers CD4 and β2-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 observed between increasing percentage levels of CD3+HLA-DR+ T lymphocytes and both declining CD4 counts (r = 0·52; P<0·001) and increasing β-microglobulin levels (r = 0·56; P<0·001). Percentage levels of CD4+HLA-DR+ and CD4+CD25+ lymphocytes were significantly higher in all HIV+ patients compared with controls (P< 0·001). Levels of activated (HLA-DR+ and CD25+) CD4+ lymphocytes showed a significant step-wise linear increase with increasing disease severity (P < 0·001). High levels of CD3+ HLA-DR+ T lymphocytes were found in a greater proportion (81·8%) of asymptomatic HIV+ patients (Centres for Disease Control (CDC) group II) than low CD4 counts (51·5%) (P<0·001). Compared with controls, HIV+ patients had higher percentage levels of CD8+HLA-DR+ lymphocytes (P<0·001), but similar levels of CD8+CD25+ lymphocytes. These results indicate that T cell activation is not only a consistent but also an early feature in HIV infection. Monitoring levels of activated T cells and their subsets is of value in assessing progression of HIV-related disease.