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Increased frequency of systemic pro-inflammatory Vδ1 + γδ T cells in HIV elite controllers correlates with gut viral load.

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  • معلومة اضافية
    • المصدر:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • الموضوع:
      Viral Load*; HIV Infections/*immunology ; HIV Infections/*virology ; HIV-1/*immunology ; Intestinal Mucosa/*virology ; Receptors, Antigen, T-Cell, gamma-delta/*metabolism ; T-Lymphocyte Subsets/*immunology ; T-Lymphocyte Subsets/*metabolism; Adult ; Cytokines/metabolism ; Female ; Host-Pathogen Interactions/immunology ; Humans ; Immunologic Memory ; Immunophenotyping ; Inflammation Mediators/metabolism ; Intestinal Mucosa/immunology ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology ; Lymphocyte Count ; Male ; Middle Aged ; Virus Replication
    • نبذة مختصرة :
      γδ T cells predominate in the intestinal mucosa and help maintain gut homeostasis and mucosal immunity. Although HIV infection significantly alters these cells, what drives these perturbations is unclear. Growing evidence suggests that impaired intestinal immune function in HIV leads to chronic immune activation and disease progression. This occurs even in HIV controllers - individuals with undetectable HIV viremia without antiretroviral therapy (ART). We show that Vδ1 + cells, a subset of γδ T cells described as being important in intestinal barrier function, increase in frequency in HIV-infected individuals, including HIV controllers. These cells resemble terminally differentiated effector memory cells, producing the pro-inflammatory cytokines IFNγ, TNFα, and MIP-1β upon stimulation. Importantly, pro-inflammatory Vδ1 + cell frequency correlates with levels of HIV RNA in intestinal tissue but not in plasma. This study supports a model in which local viral replication in the gut in HIV controllers disrupts the phenotype and function of Vδ1 + cells, a cell type involved in the maintenance of epithelial barrier integrity, and may thereby contribute to systemic immune activation and HIV disease progression.
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    • Grant Information:
      P30 DK043351 United States DK NIDDK NIH HHS
    • الرقم المعرف:
      0 (Cytokines)
      0 (Inflammation Mediators)
      0 (Receptors, Antigen, T-Cell, gamma-delta)
    • الموضوع:
      Date Created: 20181109 Date Completed: 20191028 Latest Revision: 20191107
    • الموضوع:
      20240829
    • الرقم المعرف:
      PMC6220338
    • الرقم المعرف:
      10.1038/s41598-018-34576-4
    • الرقم المعرف:
      30405182