Stimulated proliferative responses in vertically HIV-infected children on HAART correlate with clinical and immunological markers

Abstract

The objective of the study was to investigate the relationship between various CD4+ T cell subsets and the ability of peripheral blood mononuclear cells (PBMC) to proliferate to several stimuli in vertically human immunodeficiency virus type 1 (HIV-1)-infected children. We studied 29 HIV-1-infected children on highly active antiretroviral therapy (HAART) (median duration: 12.3 months). T cell subsets were determined by flow cytometry. Plasma viral load (VL) was quantified using a standardized molecular method. Proliferative responses were evaluated by [3H]-thymidine incorporation. Decreased proliferative responses of PBMC to pokeweed mitogen (PWM) were found for HIV-1-infected children in Centers for Disease Control (CDC) clinical categories B and C when compared to the control group (P < 0.05). Similarly, children with ≤ 15% CD4+ T cells showed a decrease in proliferative responses to PWM (P < 0.01), anti-CD3 + anti-CD28 (P < 0.01) and phytohaemagglutinin (PHA) (P < 0.05) with respect to the control group and to children with CD4+ T cells ≥25%. Proliferative responses to PWM, anti-CD3+, anti-CD28 and PHA had a statistically significant positive correlation with CD3+/mm3, CD4+/mm3, % CD4 T cells, CD4/CD8 ratio and the percentage of naive T cell subsets (CD4+CD45RO-HLA-DR-, CD4+ CD45RA+ CD62L+, CD4+ CD45RA+), CD4+ CD62L+ and CD4+ T cells co-expressing CD38+ (CD4+ HLA-DR-CD38+, CD4+ CD38+). Moreover, we found a negative correlation between PBMC proliferative responses and % CD8 T cells, memory, memory-activated and activated CD4+ T cell subsets. Lower proliferative responses to PWM (P < 0.01) and PHA (P < 0.01) were associated with higher VL. Our data show that higher proliferative responses to PWM, anti-CD3 + anti-CD28 and PHA are associated with both non-activated and naive CD4+ T cell subsets in HIV-1-infected children on HAART.