Low Levels of Peripheral CD161++CD8+ Mucosal Associated Invariant T (MAIT) Cells Are Found in HIV and HIV/TB Co-Infection

PLOS ONE, Dec 2019

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 = 13), latent MTB infection (LTBI) only (n = 14), pulmonary tuberculosis (TB) only (n = 9), HIV only (n = 16), HIV and LTBI co-infection (n = 13) and HIV and TB co-infection (n = 15). 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.

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Low Levels of Peripheral CD161++CD8+ Mucosal Associated Invariant T (MAIT) Cells Are Found in HIV and HIV/TB Co-Infection

et al. (2013) Low Levels of Peripheral CD161++CD8+ Mucosal Associated Invariant T (MAIT) Cells Are Found in HIV and HIV/TB Co-Infection. PLoS ONE 8(12): e83474. doi:10.1371/journal.pone.0083474 Low Levels of Peripheral CD161++CD8+ Mucosal Associated Invariant T (MAIT) Cells Are Found in HIV and HIV/TB Co-Infection Emily B. Wong 0 Ngomu Akeem Akilimali 0 Pamla Govender 0 Zuri A. Sullivan 0 Cormac Cosgrove 0 Mona Pillay 0 David M. Lewinsohn 0 William R. Bishai 0 Bruce D. Walker 0 Thumbi Ndung'u 0 Paul Klenerman 0 Victoria O. Kasprowicz 0 Thomas Jens Scriba, University of Cape Town, South Africa 0 1 KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa, 2 Division of Infectious Diseases, Massachusetts General Hospital , Boston , Massachusetts, United States of America, 3 HIV Pathogenesis Programme, University of KwaZulu-Natal , Durban , South Africa , 4 Division of Infectious Diseases, Johns Hopkins School of Medicine , Baltimore , Maryland, United States of America, 5 Peter Medawar Building for Pathogen Research, University of Oxford , Oxford , United Kingdom , 6 Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University , Portland, Oregon , United States of America, 7 Portland Veterans Administration Medical Center , Portland, Oregon , United States of America, 8 The Ragon Institute of MGH, MIT, and Harvard, Harvard Medical School , Cambridge, Massachusetts , United States of America, 9 Max Planck Institute for Infection Biology , Berlin , Germany 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 = 13), latent MTB infection (LTBI) only (n = 14), pulmonary tuberculosis (TB) only (n = 9), HIV only (n = 16), HIV and LTBI co-infection (n = 13) and HIV and TB co-infection (n = 15). 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 Va7.2. 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. - Funding: The authors would like to thank the following funders: the Howard Hughes Medical Institute (HHMI), the KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), the Harvard University CFAR grant (P30 AI060354), the National Institutes of Health (NIH) (grant AI 097138 and AI 007387), the Wellcome Trust (WT019663MA), the Oxford Martin School, the NIAID U19 Bio-defense Program (NIH NIAID 1U19AI082630-01), and the NIHR Biomedical Research Centre, Oxford. PK is an NIHR Senior Investigator. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. CD161++ CD8+ T cells have recently been brought to the forefront of research on the cellular immune response to a number of infectious diseases [1] [2,3]. Northfield et al reported that CD161 expression indicates a unique pattern of CD8+ T cell differentiation, tightly linked to co-expression of CXCR6 (a chemokine receptor with a major role in liver homing)[1]. Other studies reported two sub-populations of CD161 cells based on staining intensity [2]. The CD161++CD8+ T cell population, which expresses high levels of the C-type lectin CD161 on the cell surface, is noted for its ability to produce IL-17A and IL-22 (in addition to TNF-alpha and IFN-gamma), cytokines important in the maintenance of mucosal integrity and antibacterial immunity [2,47]. In addition thi (...truncated)


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Emily B. Wong, Ngomu Akeem Akilimali, Pamla Govender, Zuri A. Sullivan, Cormac Cosgrove, Mona Pillay, David M. Lewinsohn, William R. Bishai, Bruce D. Walker, Thumbi Ndung'u, Paul Klenerman, Victoria O. Kasprowicz. Low Levels of Peripheral CD161++CD8+ Mucosal Associated Invariant T (MAIT) Cells Are Found in HIV and HIV/TB Co-Infection, PLOS ONE, 2013, 12, DOI: 10.1371/journal.pone.0083474