Reduction in Interleukin-2-Producing Cells but not Th1 to Th2 Shift in Moderate and Advanced Stages of Human Immunodeficiency Virus Type-1-Infection: Direct Analysis of Intracellular Cytokine Concentrations in CD4+ CD8- T Cells

Abstract

Previous studies have suggested that CD4⁺ T lymphocytes shift from the Th1 type to the Th2 type during disease progression in patients with the human immunodeficiency virus type-1 (HIV-1). In the present study, we used a modified method that allowed a direct measurement of intracellular cytokines in CD4⁺ CD8⁻ T cells. A total of 48 HIV-1-infected (HIV+) and 16 HIV-1-uninfected (HIV-) individuals were studied. The percentages of CD4⁺ CD8⁻ T cells producing interleukin-2 (IL-2), interferon-γ (IFN-γ), interleukin-4 (IL-4), or interleukin-5 (IL-5) in HIV+ and HIV- subjects were 23.6% versus 34.9% (P < 0.01), 13.7% versus 13.2%, 1.3% versus 1.0%, and 1.2% versus 0.9%, respectively. The population of IL-2-producing cells decreased proportionately with reductions in CD4 counts (< 200/mm³, 200–500/mm³, and > 500/mm³ to 18.0%, 23.5%, and 30.5%, P < 0.05, respectively). There was an inverse correlation between the percentage of IL-2-producing cells and plasma viral load (r = − 0.446, P < 0.05). However, the percentages of CD4⁺ CD8⁻ T cells producing other cytokines were not different between HIV+ and HIV−. Our cross-sectional study demonstrated a decrease in IL-2-producing cells but not the Th1 to the Th2 shift in the CD4⁺ CD8⁻ T cell population in the moderate and advanced stages of HIV-1-infection.