title: Low levels of peripheral CD161++CD8+ mucosal associated invariant T (MAIT) cells are found in HIV and HIV/TB co-infection.
abstract: BACKGROUND
  High expression of CD161 on CD8+ T cells is associated with a population of cells thought to play a role in mucosal immunity. We wished to investigate this subset in an HIV and Mycobacterium tuberculosis (MTB) endemic African setting.
  
  
  METHODS
  A flow cytometric approach was used to assess the frequency and phenotype of CD161++CD8+ T cells. 80 individuals were recruited for cross-sectional analysis: controls (n = 18), latent MTB infection (LTBI) only (n = 16), pulmonary tuberculosis (TB) only (n = 8), HIV only (n = 13), HIV and LTBI co-infection (n = 15) and HIV and TB co-infection (n = 10). The impact of acute HIV infection was assessed in 5 individuals recruited within 3 weeks of infection. The frequency of CD161++CD8+ T cells was assessed prior to and during antiretroviral therapy (ART) in 14 HIV-positive patients.
  
  
  RESULTS
  CD161++CD8+ T cells expressed high levels of the HIV co-receptor CCR5, the tissue-homing marker CCR6, and the Mucosal-Associated Invariant T (MAIT) cell TCR Vα7.2. Acute and chronic HIV were associated with lower frequencies of CD161++CD8+ T cells, which did not correlate with CD4 count or HIV viral load. ART was not associated with an increase in CD161++CD8+ T cell frequency. There was a trend towards lower levels of CD161++CD8+ T cells in HIV-negative individuals with active and latent TB. In those co-infected with HIV and TB, CD161++CD8+ T cells were found at low levels similar to those seen in HIV mono-infection.
  
  
  CONCLUSIONS
  The frequencies and phenotype of CD161++CD8+ T cells in this South African cohort are comparable to those published in European and US cohorts. Low-levels of this population were associated with acute and chronic HIV infection. Lower levels of the tissue-trophic CD161++ CD8+ T cell population may contribute to weakened mucosal immune defense, making HIV-infected subjects more susceptible to pulmonary and gastrointestinal infections and detrimentally impacting on host defense against TB.
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa ; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Emily B
authors.initials: EB
authors.lastname: Wong
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa ; HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Ngomu Akeem
authors.initials: NA
authors.lastname: Akilimali
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa ; HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Pamla
authors.initials: P
authors.lastname: Govender
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa ; Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Zuri A
authors.initials: ZA
authors.lastname: Sullivan
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
authors.forename: Cormac
authors.initials: C
authors.lastname: Cosgrove
authors.affiliation: HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Mona
authors.initials: M
authors.lastname: Pillay
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon, United States of America ; Portland Veterans Administration Medical Center, Portland, Oregon, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Lewinsohn
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa ; Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: William R
authors.initials: WR
authors.lastname: Bishai
authors.affiliation: HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa ; The Ragon Institute of MGH, Massachusetts Institute of Technology, and Harvard, Harvard Medical School, Cambridge, Massachusetts, United States of America.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa ; HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa ; The Ragon Institute of MGH, Massachusetts Institute of Technology, and Harvard, Harvard Medical School, Cambridge, Massachusetts, United States of America ; Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa ; HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa ; The Ragon Institute of MGH, Massachusetts Institute of Technology, and Harvard, Harvard Medical School, Cambridge, Massachusetts, United States of America.
authors.forename: Victoria O
authors.initials: VO
authors.lastname: Kasprowicz
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D055985:Latent Tuberculosis / Q000150:complications / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism*; D013019:South Africa; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000276:immunology*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; C527203:KLRB1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B