title: HIV-Infected Children Have Lower Frequencies of CD8+ Mucosal-Associated Invariant T (MAIT) Cells that Correlate with Innate, Th17 and Th22 Cell Subsets.
abstract: Mucosal-associated invariant T cells (MAIT) are innate T cells restricted by major histocompatibility related molecule 1 (MR1) presenting riboflavin metabolite ligands derived from microbes. Specificity to riboflavin metabolites confers MAIT cells a broad array of host-protective activity against gram-negative and -positive bacteria, mycobacteria, and fungal pathogens. MAIT cells are present at low levels in the peripheral blood of neonates and gradually expand to relatively abundant levels during childhood. Despite no anti-viral activity, MAIT cells are depleted early and irreversibly in HIV infected adults. Such loss or impaired expansion of MAIT cells in HIV-positive children may render them more susceptible to common childhood illnesses and opportunistic infections. In this study we evaluated the frequency of MAIT cells in perinatally HIV-infected children, their response to antiretroviral treatment and their associations with HIV clinical status and related innate and adaptive immune cell subsets with potent antibacterial effector functions. We found HIV+ children between ages 3 to 18 years have significantly decreased CD8+ MAIT cell frequencies compared to uninfected healthy children. Remarkably, CD8 MAIT levels gradually increased with antiretroviral therapy, with greater recovery when treatment is initiated at a young age. Moreover, diminished CD8+ MAIT cell frequencies are associated with low CD4:CD8 ratios and elevated sCD14, suggesting a link with HIV disease progression. Last, CD8+ MAIT cell levels tightly correlate with other antibacterial and mucosa-protective immune subsets, namely, neutrophils, innate-like T cells, and Th17 and Th22 cells. Together these findings suggest that low frequencies of MAIT cells in HIV positive children are part of a concerted disruption to the innate and adaptive immune compartments specialized in sensing and responding to pathogenic or commensal bacteria.
authors: New York University School of Medicine, Department of Pediatrics, Division of Infectious Diseases and Immunology, New York, NY, United States of America.
authors: Alka
authors: http://orcid.org/0000-0002-7316-4300
authors: A
authors: Khaitan
authors: New York University School of Medicine, Department of Pediatrics, Division of Infectious Diseases and Immunology, New York, NY, United States of America.
authors: Max
authors: M
authors: Kilberg
authors: New York University, Department of Microbiology, New York, NY, United States of America.
authors: Adam
authors: A
authors: Kravietz
authors: New York University School of Medicine, Department of Pediatrics, Division of Infectious Diseases and Immunology, New York, NY, United States of America.
authors: Tiina
authors: T
authors: Ilmet
authors: New York University, Department of Microbiology, New York, NY, United States of America.|The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States of America.
authors: Cihan
authors: C
authors: Tastan
authors: Bomu Hospital, Mombasa, Kenya.
authors: Mussa
authors: M
authors: Mwamzuka
authors: Bomu Hospital, Mombasa, Kenya.
authors: Fatma
authors: F
authors: Marshed
authors: New York University, Division of Biostatistics, Department of Population Health, Department of Environmental Medicine, New York, NY, United States of America.
authors: Mengling
authors: M
authors: Liu
authors: Bomu Hospital, Mombasa, Kenya.
authors: Aabid
authors: A
authors: Ahmed
authors: New York University School of Medicine, Department of Pediatrics, Division of Infectious Diseases and Immunology, New York, NY, United States of America.
authors: William
authors: W
authors: Borkowsky
authors: New York University, Department of Microbiology, New York, NY, United States of America.|The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States of America.
authors: Derya
authors: D
authors: Unutmaz
mesh_terms: D000293:Adolescent; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000097:blood*; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D000072336:Mucosal-Associated Invariant T Cells / Q000166:cytology*; D058504:Th17 Cells / Q000166:cytology*