Stereotypic Expansion of T Regulatory and Th17 Cells during Infancy Is Disrupted by HIV Exposure and Gut Epithelial Damage.

Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE

Publication: Bethesda, MD : American Association of Immunologists
Original Publication: Baltimore : Williams & Wilkins, c1950-

HIV Infections/*immunology ; HIV-1/*physiology ; Intestinal Mucosa/*physiology ; Prenatal Exposure Delayed Effects/*immunology ; T-Lymphocytes, Regulatory/*immunology ; Th17 Cells/*immunology; Cell Proliferation ; Child, Preschool ; Female ; Homeostasis ; Humans ; Infant ; Infant, Newborn ; Lymphocyte Activation ; Lymphopenia ; Male ; Pregnancy

Few studies have investigated immune cell ontogeny throughout the neonatal and early pediatric period, when there is often increased vulnerability to infections. In this study, we evaluated the dynamics of two critical T cell populations, T regulatory (Treg) cells and Th17 cells, over the first 36 wk of human life. First, we observed distinct CD4 ⁺ T cells phenotypes between cord blood and peripheral blood, collected within 12 h of birth, showing that cord blood is not a surrogate for newborn blood. Second, both Treg and Th17 cells expanded in a synchronous fashion over 36 wk of life. However, comparing infants exposed to HIV in utero, but remaining uninfected, with HIV-unexposed uninfected control infants, there was a lower frequency of peripheral blood Treg cells at birth, resulting in a delayed expansion, and then declining again at 36 wk. Focusing on birth events, we found that Treg cells coexpressing CCR4 and α4β7 inversely correlated with plasma concentrations of CCL17 (the ligand for CCR4) and intestinal fatty acid binding protein, IL-7, and CCL20. This was in contrast with Th17 cells, which showed a positive association with these plasma analytes. Thus, despite the stereotypic expansion of both cell subsets over the first few months of life, there was a disruption in the balance of Th17 to Treg cells at birth likely being a result of gut damage and homing of newborn Treg cells from the blood circulation to the gut.
(Copyright © 2021 by The American Association of Immunologists, Inc.)

Comment in: J Immunol. 2022 Jan 1;208(1):1-2. doi: 10.4049/jimmunol.2190023. (PMID: 34933943)

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R01 HD102050 United States HD NICHD NIH HHS; R21 HD083344 United States HD NICHD NIH HHS; R21 HD103498 United States HD NICHD NIH HHS; U01 AI131302 United States AI NIAID NIH HHS

Date Created: 20211125 Date Completed: 20220111 Latest Revision: 20241029

20241029

PMC8702481

10.4049/jimmunol.2100503

34819390