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

Abstract

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 Th₁ (CD183⁺ CD194^- CD196^- /CXCR3⁺ CCR4^- CCR6^- ), Th₂ (CD183^- CD194⁺ CD196^- /CXCR3^- CCR4⁺ CCR6^- ), Th₁₇ (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 Th₁ CD4⁺ T cells in vitro.

Results: Lower percentages of differentiated Th₁ , Th₂ , 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 Th₁ 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 Th₁ /Th₂ /Th₁₇ and CD4⁺ CD25⁺⁺ T cells, but the intrinsic abilities of CD4⁺ T cells to acquire a Th₁ profile are not affected by the adverse maternal milieu during development.

Keywords: HIV-exposed uninfected newborns; Th cells; Th1/Th2/Th17/Treg/CD4+CD25++ T cells and Th1 differentiation.