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.
Highlights
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]
Mucosal-Associated Invariant T (MAIT) recognize bacterial riboflavin metabolite ligands presented by the MHC-related protein 1 (MR1) and are activated by pathogens including Escherichia coli, Candida albicans and Mycobacterium tuberculosis (MTB) [10,11])
Higher expression of CCR5, and CCR6 were observed on CD161++ CD8+ T cells compared to CD161+ CD8+ T cells (CCR5: p,0.0001 and CCR6: p,0.0001) and CD161CD8+ T cells (CCR5: p,0.0001 and CCR6: p,0.0001) (Fig. 1B, Fig. 1C)
Summary
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]. 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 [2,4,5,6,7]. In addition this population, that expresses tissue-homing markers including CCR6 and CXCR6, is enriched in tissue samples including the liver and the joints [2]. We wished to investigate this subset in an HIV and Mycobacterium tuberculosis (MTB) endemic African setting
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