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.


CONCLUSIONS
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.
Resino
S
S
Department of Immunology, General University Hospital Gregorio Marañón, Madrid, Spain.
Bellón
J M
JM
Gurbindo
D
D
Muñoz-Fernández
M A
MA
D016516:CD4-CD8 Ratio; D018925:Chemokines / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission; D015497:HIV-1; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D007372:Interferons / Q000096:biosynthesis* / Q000097:blood; D007378:Interleukins / Q000096:biosynthesis* / Q000097:blood; D009000:Monocytes / Q000378:metabolism; D011237:Predictive Value of Tests; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism
D018925:Chemokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons