Impaired T helper cell responses in human immunodeficiency virus‐exposed uninfected newborns

INTRODUCTION: HIV‐exposed uninfected (HEU) newborns suffer from higher risks of opportunistic infections during the first months of life compared to HIV‐unexposed uninfected (HUU) newborns. Alterations in thymic mass, amounts of T helper (Th) cells, T‐cell receptor diversity, and activation markers have been found in HEU newborns, suggesting alterations in T cell ontogeny and differentiation. However, little is known about the ability of these cells to produce specialized Th responses from CD4(+) T cells. METHOD: To characterize the Th cell profile, we evaluated the frequency of Th(1) (CD183(+)CD194(−)CD196(−)/CXCR3(+)CCR4(−)CCR6(−)), Th(2) (CD183(−)CD194(+)CD196(−)/CXCR3(−)CCR4(+)CCR6(−)), Th(17) (CD183(−)CD194(+)CD196(+)/CXCR3(−)CCR4(+)CCR6(+)), and CD4(+)CD25(++) blood T‐cell phenotypes in 50 HEU and 25 HUU newborns. Early activation markers on CD4(+) T cells and the Th cytokine profile produced from mononuclear cells under polyclonal T cell stimulation were also studied. Additionally, we probed the ability of CD4(+) T cells to differentiate into interferon (IFN)‐γ‐producing Th(1) CD4(+) T cells in vitro. RESULTS: Lower percentages of differentiated Th(1), Th(2), Th(17,) and CD4(+)CD25(++) T cells were found in blood from HEU newborns than in blood from HUU newborns. However, polyclonally stimulated Th cells showed a similar ability to express CD69 and CD279 but produced less secreted interleukin (IL)‐2 and IL‐4. Interestingly, under Th(1) differentiation conditions, the percentages of CD4(+)IFN‐γ(+) T cells and soluble IFN‐γ were higher in HEU newborns than in HUU newborns. CONCLUSION: HEU neonates are born with reduced proportions of differentiated Th(1)/Th(2)/Th(17) and CD4(+)CD25(++) T cells, but the intrinsic abilities of CD4(+) T cells to acquire a Th(1) profile are not affected by the adverse maternal milieu during development.