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 (CD183 CD194 CD196 /CXCR3 CCR4 CCR6 ), Th (CD183 CD194 CD196 /CXCR3 CCR4 CCR6 ), Th (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 CD4 T cells in vitro.

RESULTS

Lower percentages of differentiated Th , Th , Th 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 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 /Th /Th and CD4 CD25 T cells, but the intrinsic abilities of CD4 T cells to acquire a Th profile are not affected by the adverse maternal milieu during development.