Abstract
Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU) infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU) infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42) and HU (n = 28) Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of vaccine efficacy and T-cell immunity in this vulnerable population is warranted.
Highlights
Due to the success of antiretroviral therapy (ART) strategies, mother-to-child transmission of HIV-1 has been virtually eliminated in countries with universal access to health care and is in steep decline in many sub-Saharan African countries[1,2]
We assessed alterations in the T-cell compartment of HIV-exposed uninfected (HEU) infants focusing on ex vivo phenotypes and functional responses to the vaccine antigens purified protein derivative (PPD) and TT and polyclonal stimulation
In accordance with recent findings[34], ex vivo analyses indicated that immune activation, Treg frequencies and the frequency of memory subsets were closely matched between groups
Summary
Due to the success of antiretroviral therapy (ART) strategies, mother-to-child transmission of HIV-1 has been virtually eliminated in countries with universal access to health care and is in steep decline in many sub-Saharan African countries[1,2]. Being born into an HIV-infected household has clear implications regarding infant care. Mothers may themselves be ill or suffering economic consequences of their infection. HEU infants may experience heightened vertical exposure to maternal co-infections such as cytomegalovirus (CMV) and Mycobacterium tuberculosis[7]. In utero exposure to antiretroviral drugs and maternal immune system perturbations, including inflammation from HIV-1 infection during foetal and/or neonatal development may have lasting effects on infant immunity
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