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

Abstract

BackgroundHigh 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.MethodsA 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.ResultsCD161++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.ConclusionsThe 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.

Mucosal-associated invariant T cell–rich congenic mouse strain allows functional evaluation

“…The frequency of MAITs is also modified in nonbacterial diseases: increased in recently diagnosed multiple sclerosis patients (12,13), but decreased in obesity, type-2 diabetes (14), inflammatory bowel disease (15), and HIV (16)(17)(18)(19).…”

CCR6/CCL20 chemokine axis in human immunodeficiency virus immunity and pathogenesis

“…CD8 + CCR6 + mucosal-associated invariant T cells in infected HIV patients tend to have lower surface CCR6 expression compared with healthy control mucosalassociated invariant T cells [56,57], possibly leading to their failure to migrate to key immunological sites.…”

The role of mucosal‐associated invariant T cells in infectious diseases

“…10,[16][17][18][19] MAIT cell activation can result from either TCR-dependent signalling (triggered by ligand presented on MR1 by antigen-presenting cells) or from TCR-independent cytokine signalling. [20][21][22][23] Like other 'innate-like' lymphocytes including invariant natural killer T ª 2016 John Wiley & Sons Ltd, Immunology, 150, [45][46][47][48][49][50][51][52][53][54] cells and natural killer cells, MAIT cells respond rapidly to activation by producing cytokines and cytolytic products. Upon TCR-dependent or TCR-independent activation, MAIT cells produce interferon-c (IFN-c), tumour necrosis factor-a (TNF-a), cytolytic products (perforin, granulysin and granzymes) and degranulate (exposing CD107a to the cell surface).…”

“…21 Recently, however, a report by van Wilgenburg et al 48 has demonstrated that MAIT cells can be activated in an MR1-independent cytokine-driven manner by dengue virus, hepatitis C virus and influenza virus. Interleukin-18 signalling is most central to MAIT activation in these settings, though the effects of other virally driven cytokines [49][50][51][52][53][54] Interestingly, the degree of MAIT cell depletion does not correlate to the usual markers of HIV disease progression, including the degree of peripheral CD4 + T-cell depletion or the level of viral replication in the blood (HIV viral load). 51,54 Even individuals who appear to have a natural ability to control HIV infection (long-term non-progressors and elite controllers) have been found to experience similar levels of MAIT cell depletion to those observed in people with chronic progressive HIV infection.…”

“…Interleukin-18 signalling is most central to MAIT activation in these settings, though the effects of other virally driven cytokines [49][50][51][52][53][54] Interestingly, the degree of MAIT cell depletion does not correlate to the usual markers of HIV disease progression, including the degree of peripheral CD4 + T-cell depletion or the level of viral replication in the blood (HIV viral load). 51,54 Even individuals who appear to have a natural ability to control HIV infection (long-term non-progressors and elite controllers) have been found to experience similar levels of MAIT cell depletion to those observed in people with chronic progressive HIV infection. 50 Leeansyah et al 26,53 have found that the MAIT cells that remain in the peripheral circulation of patients with HIV are functionally impaired compared with MAIT cells from healthy people.…”