Selective increase of activation antigens HLA-DR and CD38 on CD4+ CD45RO+ T lymphocytes during HIV-1 infection

Infection with HIV results in a progressive depletion of CD4(+) T cells and leads to significant in vivo lymphocyte phenotype changes. In this regard, the expression of HLA-DR and CD38 on CD8(+) T cells has been shown to increase dramatically with disease progression. We investigated the expression of both activation markers on CD4(+) T cells in HIV-1-infected subjects at different clinical stages of infection and compared the in vivo activation of CD4(+) T cells with parameters of viral activity and CD8(+) T cell activation. Fresh peripheral venous blood was obtained from 54 HIV-infected subjects and from 28 uninfected healthy controls. Three-colour immunophenotyping of the CD4(+) T cell subset showed that the proportion of CD4(+) T cells expressing HLA-DR (10% in HIV-negative controls) or CD38 (62% in HIV-negative controls) was higher in asymptomatic (P < 0.05 for CD38) and symptomatic (P < 0.001 for HLA-DR and CD38) HIV-infected subjects than in controls, whereas the proportion of CD4(+) T cells expressing CD45RO (54% in controls) remained relatively unchanged. Simultaneous expression of HLA-DR and CD38 on CD4(+) T cells increased from 2.3% in controls to 11% (P < 0.001) in asymptomatic and 22% (P < 0.001) in symptomatic HIV-infected subjects. This relative increase of CD38 and HLA-DR expression occurred mainly on CD4(+) T cells co-expressing CD45RO. Changes in expression of HLA-DR and CD38 on CD4(+) T cells correlated with similar changes on CD8(+) T lymphocytes, with the presence of HIV antigen in the circulation, and with the disease stage of HIV infection.