Disruption in cytokine and chemokine production by T-cells in vertically HIV-1-infected children

This study measured cytokine production by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) from 55 human immunodeficiency virus (HIV)-infected children born to HIV-infected mothers, and compared it with vertically exposed but uninfected age-matched children. A significant defect was observed in Th1 cytokine production interferon-gamma and interleukin-2 (IL-2)] in HIV-infected children compared with controls, but without a concomitant increase in Th2 cytokines. Indeed, IL-5 and IL-10 production was even lower in HIV-infected children than in controls, with the decrease in IL-5 being the best predictive marker of immunodeficiency. In addition, an increased release of tumour necrosis factor-alpha (TNF-alpha) that correlated well with CD4+ levels, and a positive correlation of the TNF-alpha/IL-10 ratio with disease progression was observed. A correlation between AIDS-free status and higher %CD4+ and %CD8+ T-lymphocytes and RANTES (regulated on activation, normal T-cell expressed and secreted) production was also found. Conclusion: A dysfunctional cytokine production of PBMCs was observed in HIV-infected children in both Th1 and Th2 cytokines due to quantitative and qualitative defects induced by HIV-1. An important observation was an increased RANTES production associated with viral isolates of NSI/R5 phenotype and S/L kinetics.