Ontogeny of CD4
            <sup>+</sup>
            T Lymphocytes with Phenotypic Susceptibility to HIV-1 during Exclusive and Non-Exclusive Breastfeeding in HIV-1-exposed Ugandan Infants

McFarland, Elizabeth J.; Powell, Tina M.; Onyango‐Makumbi, Carolyne; Zhang, Weimin; Melander, Kelsey; Naluyima, Prossy; Okurut, Samuel; Eller, Michael A.; Fowler, Mary Glenn; Janoff, Edward N.

doi:10.1093/infdis/jiw553

Cited by 3 publications

(4 citation statements)

References 48 publications

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“…Although we did not measure HIV target cells at the mucosa, higher buccal mucosal transcript levels of chemokines capable of attracting T cells in NEBF infants suggest that these cells are likely homing to this site. Consistent with this, increased CD4+CCR5+ cells expressing the mucosal homing marker β7 were present in Ugandan NEBF infants, providing evidence that nonexclusive breastfeeding increases HIV target cells at mucosal sites [11].…”

Section: Discussionsupporting

confidence: 58%

“…An alternative hypothesis that nonexclusive breastfeeding increases translocation of microbes across the gastrointestinal mucosa into systemic circulation has shown conflicting results [9,10]. Recently, NEBF infants in Uganda had higher levels of gut-homing T cells, although the cause of this increase was not identified [11]. To date, no study has systematically examined infant factors that influence susceptibility to HIV.…”

mentioning

confidence: 99%

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Feeding-Related Gut Microbial Composition Associates With Peripheral T-Cell Activation and Mucosal Gene Expression in African Infants

Wood

Brown

Lennard

et al. 2018

Clinical Infectious Diseases

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Section: Discussionsupporting

confidence: 58%

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confidence: 99%

Feeding-Related Gut Microbial Composition Associates With Peripheral T-Cell Activation and Mucosal Gene Expression in African Infants

Wood

Brown

Lennard

et al. 2018

Clinical Infectious Diseases

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“…uninfected infants also have high levels of immune activation [12-15] and this was evidenced in our study as well. The expression of activation markers on CD4+ and CD8+ T cells increases rapidly from birth in the first few weeks of life in the HIV-exposed infants [16, 17]. Such high immune activation has been hypothesized to contribute to ongoing inflammation and poor health outcomes of such infants [18], possibly mediated through intestinal mucosal damage [11, 17]…”

Section: Discussionmentioning

confidence: 99%

Potential Role of Regulatory T Cells in Mother-to-Child Transmission of HIV

Keßler

2019

CHR

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Background:Mother-to-child transmission of HIV-1 occurs in a minority of HIVinfected mother-infant pairs, even without any interventions. The mechanisms that protect the majority of HIV-exposed infants from infection are unclear. T regulatory cells (Treg) have important immunomodulatory functions, but their role in the fetus as well as in mother-to-child transmission of HIV is under-studied.Methods:We studied available cryopreserved peripheral blood mononuclear cells from HIVexposed infants from the Breastfeeding, Antiretrovirals and Nutrition (BAN) Study cohort in Malawi: 64 infants were HIV-uninfected and 28 infants were HIV-infected at birth. We quantified the frequency of Treg cells (CD4+CD25+FoxP3+), and activated CD4+ and CD8+ T cells (CD38+ HLADR+) by flow cytometry at birth, 6 weeks and 6, 9 and 12 months of age. Descriptive statistics were performed to describe the distributions of these lymphocyte markers according to the HIV infection status; and Student’s t tests and Wilcoxon-Rank Sum tests were performed to compare HIVinfected and uninfected infants.Results:T cell activation increased rapidly in the first 6 weeks of life, more pronounced on CD8+ T cells; a further increase in activation was observed at the time of weaning from breastfeeding at 6 months of age. In contrast, the frequency of Treg was stable over the first 6 weeks of life (median, 0.5%), slightly decreased between 6 weeks and 6 months (median at 6 months, 0.3%) and then slightly increased between 6 months (time of weaning) and 12 months of age (median, 0.45%). HIVinfected infants had significantly higher frequencies of activated T cells than uninfected infants (P < 0.01). At the time of birth, HIV-exposed uninfected infants had higher levels of Treg, compared to infants infected in utero, even though this did not reach statistical significance in this small sample size (P = 0.08).Conclusion:This study provides initial evidence that Treg may play a role in preventing mother-tochild transmission of HIV, likely by suppressing immune activation in the fetus and infant, and needs to be substantiated in a larger study. Better characterization of the role of Treg in fetal and neonatal immunity may provide a valuable complementary approach to achieve eradication of mother-to-child transmission of HIV.

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“…102 In turn, the low microbial diversity in nonexclusively breastfed infants was associated with higher gut-homing ( α 4 β 7 + ) immune activated lymphocytes (CCR5 + HLA-DR + CD25 + ). 102,103 Additionally, changes in microbial profiles in the gut of HEU infants are independent of feeding choice but appear to be influenced by maternal HIV status. Compared with HIV-unexposed infants, gut microbiota of breastfed HEU infants have lower α -diversity at 6 weeks of life.…”

Section: Relationship Of Breastfeeding and Microbiota Composition Of mentioning

confidence: 99%

Impact of maternal HIV exposure, feeding status, and microbiome on infant cellular immunity

Dzanibe

Jaspan

Zulu

et al. 2018

Journal of Leukocyte Biology

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At least one-third of infants born in sub-Saharan Africa have been exposed to the effects of maternal HIV infection and antiretroviral treatment. Intrauterine HIV exposure is associated with increased rates of morbidity and mortality in children. Although the mechanisms responsible for poor infant health with HIV-1 exposure are likely to be multifactorial, we posit that the maternal environment during gestation and in the perinatal period results in altered infant immunity and is possibly the strongest contributing factor responsible for the disproportionally high infectious events among HIV-exposed infants who remain HIV uninfected. This review provides a synthesis of studies reporting the impact of intrauterine HIV exposure, feeding practices, and microbiota on immune ontogeny in the first year of life in HIV-exposed uninfected infants.

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Ontogeny of CD4 ⁺ T Lymphocytes with Phenotypic Susceptibility to HIV-1 during Exclusive and Non-Exclusive Breastfeeding in HIV-1-exposed Ugandan Infants

Abstract: The T-cell phenotype associated with susceptibility to HIV-1 infection (CCR5+, gut-homing, CM CD4+ T cells) was preferentially expressed in nonexclusively breastfed infants, a group of infants at increased risk for HIV-1 acquisition.

Cited by 3 publications

References 48 publications

Feeding-Related Gut Microbial Composition Associates With Peripheral T-Cell Activation and Mucosal Gene Expression in African Infants

Feeding-Related Gut Microbial Composition Associates With Peripheral T-Cell Activation and Mucosal Gene Expression in African Infants

Potential Role of Regulatory T Cells in Mother-to-Child Transmission of HIV

Impact of maternal HIV exposure, feeding status, and microbiome on infant cellular immunity

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Ontogeny of CD4 + T Lymphocytes with Phenotypic Susceptibility to HIV-1 during Exclusive and Non-Exclusive Breastfeeding in HIV-1-exposed Ugandan Infants

Abstract: The T-cell phenotype associated with susceptibility to HIV-1 infection (CCR5+, gut-homing, CM CD4+ T cells) was preferentially expressed in nonexclusively breastfed infants, a group of infants at increased risk for HIV-1 acquisition.

Cited by 3 publications

References 48 publications

Feeding-Related Gut Microbial Composition Associates With Peripheral T-Cell Activation and Mucosal Gene Expression in African Infants

Feeding-Related Gut Microbial Composition Associates With Peripheral T-Cell Activation and Mucosal Gene Expression in African Infants

Potential Role of Regulatory T Cells in Mother-to-Child Transmission of HIV

Impact of maternal HIV exposure, feeding status, and microbiome on infant cellular immunity

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Product

Resources

About

Ontogeny of CD4 ⁺ T Lymphocytes with Phenotypic Susceptibility to HIV-1 during Exclusive and Non-Exclusive Breastfeeding in HIV-1-exposed Ugandan Infants