Expression of the CD8αβ-Heterodimer on CD8+ T Lymphocytes in Peripheral Blood Lymphocytes of Human Immunodeficiency Virus− and Human Immunodeficiency Virus+Individuals

Abstract

CD8+ T lymphocytes play a pivotal role in controlling human immunodeficiency virus (HIV)-1 replication in vivo. We have performed four-color flow cytometric analysis of CD8+peripheral blood lymphocytes (PBL) from 21 HIV-1 seronegative and 103 seropositive individuals to explore the phenotypic heterogeneity of CD8β-chain expression on CD8+ T lymphocytes and to clarify how its expression on CD8+ T lymphocytes may relate to acquired immunodeficiency syndrome (AIDS) clinical progression. We showed that the single monoclonal antibody (MoAb) 2ST8-5H7, directed against the CD8αβ-heterodimer, identifies CD8+ T lymphocytes as effectively as the conventional combination of anti-CD3 and anti-CD8α antibodies. However, we detected a significantly lower mean fluorescence (MF) of anti-CD8αβ staining on PBL from HIV-1 seropositive donors as compared with seronegative donors. In fact, CD8+ T lymphocytes from HIV-1–infected individuals with the lowest CD4 counts showed the lowest levels of CD8αβ MF. To explore further this change in CD8αβ expression, we assessed the expression of 14 different cell surface molecules on CD8αβ+ T lymphocytes of PBL from 11 HIV-1 seronegative and 22 HIV-1 seropositive individuals. The MF of anti-CD8αβ staining was significantly reduced on CD8+T lymphocyte subsets that showed immunophenotypic evidence of activation. The subset of lymphocytes expressing low levels of CD8αβ expressed higher levels of activation, adhesion, and cytotoxic-associated molecules and was predominantly CD45RO+ and CD28−. Finally, we monitored the expression of the CD8αβ-heterodimer on PBL of eight HIV-1–infected individuals over a 16-week period after the initiation of highly active antiretroviral therapy (HAART), including zidovudine (ZDV), lamivudine (3TC), and indinavir (IDV), and found a significant increase in the expression of the CD8αβ-heterodimer. These results suggest that antibodies recognizing the CD8αβ-heterodimer are useful tools to specifically identify CD8+ T lymphocytes. Moreover, the quantitative monitoring of CD8αβ expression allows the detection of discrete CD8+ T lymphocyte subsets and may be useful for assessing the immune status of individuals infected with HIV-1.