Early and nonreversible decrease of CD161++ /MAIT cells in HIV infection

Blood. 2013 Feb 7;121(6):951-61. doi: 10.1182/blood-2012-06-436436. Epub 2012 Dec 18.

Abstract

HIV infection is associated with immune dysfunction, perturbation of immune-cell subsets and opportunistic infections. CD161++ CD8+ T cells are a tissue-infiltrating population that produce IL17A, IL22, IFN, and TNFα, cytokines important in mucosal immunity. In adults they dominantly express the semi-invariant TCR Vα7.2, the canonical feature of mucosal associated invariant T (MAIT) cells and have been recently implicated in host defense against pathogens. We analyzed the frequency and function of CD161++ /MAIT cells in peripheral blood and tissue from patients with early stage or chronic-stage HIV infection. We show that the CD161++ /MAIT cell population is significantly decreased in early HIV infection and fails to recover despite otherwise successful treatment. We provide evidence that CD161++ /MAIT cells are not preferentially infected but may be depleted through diverse mechanisms including accumulation in tissues and activation-induced cell death. This loss may impact mucosal defense and could be important in susceptibility to specific opportunistic infections in HIV.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • Apoptosis / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology
  • Cells, Cultured
  • Cohort Studies
  • Escherichia coli / immunology
  • Female
  • Flow Cytometry
  • HIV / drug effects
  • HIV / immunology
  • HIV Infections / blood
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • Humans
  • Immunity, Mucosal / immunology*
  • Immunohistochemistry
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / virology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • NK Cell Lectin-Like Receptor Subfamily B / immunology*
  • NK Cell Lectin-Like Receptor Subfamily B / metabolism
  • Receptors, CCR5 / immunology
  • Receptors, CCR5 / metabolism
  • Receptors, CCR6 / immunology
  • Receptors, CCR6 / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / virology
  • Time Factors

Substances

  • Anti-HIV Agents
  • CCR6 protein, human
  • Interleukin-17
  • KLRB1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily B
  • Receptors, CCR5
  • Receptors, CCR6