The CD4−CD8−MAIT cell subpopulation is a functionally distinct subset developmentally related to the main CD8+MAIT cell pool

Dias, Joana; Boulouis, Caroline; Gorin, Jean‐Baptiste; Biggelaar, Robin H.G.A. van den; Lal, Kerri G.; Gibbs, Anna; Loh, Liyen; Gulam, Muhammad Yaaseen; Sia, Wan Rong; Bari, Sudipto; Hwang, William Ying Khee; Nixon, Douglas F.; Nguyen, Son; Betts, Michael R.; Buggert, Marcus; Eller, Michael A.; Broliden, Kristina; Tjernlund, Annelie; Sandberg, Johan K.; Leeansyah, Edwin

doi:10.1073/pnas.1812273115

Cited by 140 publications

(145 citation statements)

References 57 publications

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Section: Discussionmentioning

confidence: 65%

“…CD8 + and CD4 − CD8 − DN MAIT cells are functionally distinct subsets . In peripheral blood, the ratio of PD‐1‐expressing MAIT cells is higher in CD8 + cells than in CD4 − CD8 − DN subset . In tuberculous pleural effusions, we found that the frequency of PD‐1‐expressing CD4 − CD8 − DN MAIT cells was significantly higher than that of CD8 + MAIT cells.…”

Section: Discussionmentioning

confidence: 99%

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PD‐1‐expressing MAIT cells from patients with tuberculosis exhibit elevated production of CXCL13

Jiang

Cao

et al. 2020

Scand J Immunol

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To understand functional role of PD‐1‐expressing MAIT cells during tuberculosis infection in humans, sorted PD‐1+ and PD‐1− MAIT cells from pleural effusions of patients with pleural tuberculosis were subjected to transcriptome sequencing. PD‐1‐expressing MAIT cells were analysed by flow cytometry and their phenotypic and functional features were investigated. Transcriptome sequencing identified 144 genes that were differentially expressed between PD‐1+ and PD‐1− MAIT cells from tuberculous pleural effusions and CXCL13 was the gene with highest fold difference. The level of PD‐1‐expressing MAIT cells was associated with extent of TB infection in humans. PD‐1‐expressing MAIT cells had increased production of CXCL13 and IL‐21 as determined by flow cytometry. PD‐1highCXCR5− MAIT cells were significantly expanded in pleural effusions from patients with pleural tuberculosis as compared with those from peripheral blood of both patients with tuberculosis and healthy controls. Although PD‐1highCXCR5− MAIT cells from tuberculous pleural effusions had reduced IFN‐γ level and increased expression of Tim‐3 and GITR, they showed activated phenotype and had higher glucose uptake and lipid content. It is concluded that PD‐1‐expressing MAIT cells had reduced IFN‐γ level but increased production of both CXCL13 and IL‐21.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

PD‐1‐expressing MAIT cells from patients with tuberculosis exhibit elevated production of CXCL13

Jiang

Cao

et al. 2020

Scand J Immunol

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“…Our panel enables the analysis of CXCR5, which interacts with CXCL13. The inclusion of CD27 and CD28 in addition to CD45RA and CCR7 enables a refined delineation of memory T cell subsets (11). 1G,H).…”

Section: Introductionmentioning

confidence: 99%

OMIP‐058: 30‐Parameter Flow Cytometry Panel to Characterize iNKT, NK, Unconventional and Conventional T Cells

Liechti¹,

Roederer²

2019

Cytometry Pt A

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“…Next, we investigated the cytokine production capacity of MAIT cells by stimulating them specifically via the MR1 receptor using APCs loaded with E. coli , as previously described 16,29 . The stimulation of MAIT cells with E. coli resulted in a much more rapid loss of CD8 expression by MAIT cells than was seen in CD3+ T cells stimulated with E.coli ‐loaded APCs or PMA/ionomycin (Figure S7), which has been demonstrated before 43 . This loss of CD8 expression hindered our capacity to confidently separate CD8 + MAIT cells from DN MAIT cells.…”

Section: Resultsmentioning

confidence: 66%

645. Mucosal-Associated Invariant T cells in Renal Tissue From Patients With Recurrent Urinary Tract Infections

Terpstra

Sinnige

Remmerswaal

et al. 2018

Open Forum Infectious Diseases

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BackgroundMucosal associated invariant T (MAIT) cells are innate-like T-cells involved in the antibacterial and fungal response by recognizing riboflavin metabolites produced by these organisms. MAIT cells are present in blood and are highly abundant in the mucosa of the liver, lungs and intestines. In murine models of urinary tract infection (UTI), MAIT cells appear to migrate to the bladder and decrease the bacterial load. It is however unknown whether MAIT cells reside in the human urogenital tract and renal tissue and whether they play a role in the first-line defense against (recurrent) UTI (RUTI).MethodsWe used a fluorescently labelled MR1-tetramer in conjunction with 14-color flowcytometry to identify and characterize MAIT cells in renal allografts after allograft failure caused by RUTI (n = 6) or rejection (n = 6) and in healthy kidney tissue surgically removed because of renal cell carcinoma (adjacent nontumorous tissue) (n = 5).ResultsThe mean percentage of MAIT cells within the lymphogate was higher in the RUTI kidneys (2.24%) compared with the rejection kidneys (0.14%) and the control kidneys (0.11%) (P < 0.05).Characterization of MAIT cells was impossible in some control samples due to MAIT cells counts <25 (predefined cutoff value), therefore the control group was excluded from further statistical analysis.MAIT cells in RUTI kidneys appear to have a less activated profile compared with the rejection kidneys, with a lower expression of Ki67 (P < 0.01). Though the expression of the tissue resident marker CD69/CD103 was higher in 4/6 RUTI kidneys, this difference was not significant.ConclusionMAIT cells are present in renal tissue that is or has been subjected to an immunologic response. MAIT cells in RUTI kidneys display a more quiescent and in some samples more tissue resident phenotype than MAIT cells in rejection kidneys. These findings may suggest that (I) MAIT cells play a role in the first-line defense in the kidney and (II) that after RUTI, MAIT cells remain in renal tissue in a quiescent state. We postulate that this might be favorable in case of a second hit from an uropathogen.Figure 1.Presence and characterization of MAIT cells in renal tissue.Disclosures F. Bemelman, Astellas: We received an unrestricted grant from Astellas to establish a Biobank for patients with renal diseases. The samples described in this abstract are obtained from this Biobank., Grant recipient.

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The CD4⁻CD8⁻MAIT cell subpopulation is a functionally distinct subset developmentally related to the main CD8⁺MAIT cell pool

Cited by 140 publications

References 57 publications

PD‐1‐expressing MAIT cells from patients with tuberculosis exhibit elevated production of CXCL13

PD‐1‐expressing MAIT cells from patients with tuberculosis exhibit elevated production of CXCL13

OMIP‐058: 30‐Parameter Flow Cytometry Panel to Characterize iNKT, NK, Unconventional and Conventional T Cells

645. Mucosal-Associated Invariant T cells in Renal Tissue From Patients With Recurrent Urinary Tract Infections

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