Dataset Information

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.

SUBMITTER: Brito-Perez Y

PROVIDER: S-EPMC8589403 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Most studies examining the association of prenatal antiretroviral (ARV) exposures with congenital anomalies (CAs) in children born to human immunodeficiency virus (HIV)-infected women have been reassuring, but some evidence suggests an increased risk with specific ARV agents.To evaluate the association of in utero ARV exposures with CAs in HIV-exposed uninfected children.Prospective cohort study design. The Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring of ART Toxicities (SMARTT) Study was performed at 22 US medical centers among 2580 HIV-exposed uninfected children enrolled in the SMARTT Study between March 23, 2007, and June 18, 2012.First-trimester exposure to any ARV and to specific ARV medications.The primary end point was a CA based on physician review of infant physical examinations according to the Antiretroviral Pregnancy Registry modification of the Metropolitan Atlanta Congenital Defects Program. Rates of CAs were estimated overall and by birth year. Logistic regression models were used to evaluate the association of CAs with first-trimester ARV exposures, adjusting for demographic and maternal characteristics.Congenital anomalies occurred in 175 of 2580 children, yielding a prevalence of 6.78% (95% CI, 5.85%-7.82%); 242 major CAs were confirmed, including 72 musculoskeletal and 55 cardiovascular CAs. The prevalence of CAs increased significantly among successive birth cohorts (3.8% for children born before 2002 and up to 8.3% for those born 2008-2010). In adjusted models, no association of first-trimester exposures with CAs was found for any ARV, for combination ARV regimens, or for any drug class. No individual ARV in the reverse transcriptase inhibitor drug classes was associated with an increased risk of CAs. Among protease inhibitors, higher odds of CAs were observed for atazanavir sulfate (adjusted odds ratio [aOR], 1.95; 95% CI, 1.24-3.05) and for ritonavir used as a booster (aOR, 1.56; 95% CI, 1.11-2.20). With first-trimester atazanavir exposure, risks were highest for skin (aOR, 5.23) and musculoskeletal (aOR, 2.55) CAs.Few individual ARVs and no drug classes were associated with an increased risk of CAs in HIV-exposed infants after adjustment for calendar year and maternal characteristics. While the overall risk remained low, a relative increase was observed in successive years and with atazanavir exposure. Given the low absolute CA risk, the benefits of recommended ARV therapy use during pregnancy still outweigh such risks, although further studies are warranted.