Activation of Human Mucosal-Associated Invariant T Cells Induces CD40L-Dependent Maturation of Monocyte-Derived and Primary Dendritic Cells

Salio, Mariolina; Gasser, Olivier; Lopez, Carlos G.; Martens, Anne W. J.; Veerapen, Natacha; Gileadi, Uzi; Verter, Jacob; Napolitani, Giorgio; Anderson, Regan J.; Painter, Gavin F.; Besra, Gurdyal S.; Hermans, Ian F.; Cerundolo, Vincenzo

doi:10.4049/jimmunol.1700615

Cited by 91 publications

(115 citation statements)

References 42 publications

(49 reference statements)

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“…Besides production of cytokines and cytotoxic molecules that have direct effect on infection control, MAIT cells have role in immune regulation. It has been reported that MAIT cells drives the differentiation of inflammatory monocytes into monocyte‐derived DCs through early pulmonary GM‐CSF production during pulmonary intracellular infection and induces maturation of DCs via CD40L‐dependent pathway . It has been reported that MAIT cells promote plasmablasts of B cells and production of IgA, IgG and IgM .…”

Section: Discussionmentioning

confidence: 92%

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: 92%

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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“…is detectable in a small proportion of PB MAIT cells, 43,46 but neither CD94 nor NKG2A is found on the CD4 + subset. 50 Importantly, when compared with their CD94 − , CD56 − , and CD84 − counterparts, MAIT cells expressing these molecules more readily produce IFNin response to IL-12 and IL-18.…”

Section: Mait Cell Surface Molecules Associated With Cytotoxicitymentioning

confidence: 89%

“…For instance, CD94, which associates with NKG2A, −C, −E, and −F to recognize the MHC class Ib molecule HLA‐E, is not uniformly expressed by all PB MAIT cells . Of note, NKG2A is detectable in a small proportion of PB MAIT cells, but neither CD94 nor NKG2A is found on the CD4 + subset . Importantly, when compared with their CD94 − , CD56 − , and CD84 − counterparts, MAIT cells expressing these molecules more readily produce IFN‐γ in response to IL‐12 and IL‐18 .…”

Section: Mait Cell Surface Molecules Associated With Cytotoxicitymentioning

confidence: 99%

“…Salio et al. recently reported that MAIT cells activated by 5‐OP‐RU upregulate CD40 ligand (CD40L, CD154) and/or soluble factors that promote dendritic cell (DC) maturation and production of T H 1‐polarizing cytokines, such as IL‐12 . In turn, NK cells were consequently activated to produce IFN‐γ.…”

Section: Effector Molecules Within Mait Cells’ Lethal Arsenalmentioning

confidence: 99%

“…Being potent and prompt producers of IFN-, 12 maturation and production of T H 1-polarizing cytokines, such as IL-12. 46 In turn, NK cells were consequently activated to produce IFN-.…”

Section: Pathogen Target Cells Effector Cells a Mait Cell Lytic Profilementioning

confidence: 99%

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MAIT cell-mediated cytotoxicity: Roles in host defense and therapeutic potentials in infectious diseases and cancer

Rudak

Choi

Haeryfar

2018

Journal of Leukocyte Biology

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Mucosa-associated invariant T (MAIT) cells are unconventional, innate-like T lymphocytes that sense the presence of MHC-related protein 1 (MR1)-restricted ligands and select inflammatory cues. Consequently, they release potent immunomodulatory mediators, including IFN-γ, TNF-α, and/or IL-17. MAIT cells can also be viewed as killer cells. They display several NK cell-associated receptors, carry granules containing cytotoxic effector molecules, and swiftly upregulate perforin and granzymes upon activation. Accordingly, MAIT cells are capable of lysing MR1-expressing cells infected with a variety of pathogenic bacteria in in vitro settings and may also mount cytotoxic responses during microbial infections in vivo. Of note, MAIT cell hyperactivation during certain infections may impede their ability to elicit inflammatory and/or cytotoxic responses to secondary stimuli. In addition, MAIT cells isolated from within and from the margin of tumor masses exhibit diminished functions. We propose that MAIT cell-mediated cytotoxicity can be induced, bolstered, or restored to assist in clearing infections and potentially in reducing tumor loads. In this review, we discuss our current understanding of MAIT cells' lytic functions and highlight the pressing questions that need to be addressed in future investigations. We also offer a picture, however hypothetical at this point, of how harnessing the full cytotoxic potentials of MAIT cells may be a valuable approach in the immunotherapy of infectious and malignant diseases.

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Characterization of Human Mucosal‐associated Invariant T (MAIT) Cells

Souter

Loh

et al. 2019

CP in Immunology

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Mucosal‐associated invariant T (MAIT) cells are a subset of unconventional T cells restricted by the major histocompatibility complex (MHC) class I–like molecule MHC‐related protein 1 (MR1). MAIT cells are found throughout the body, especially in human blood and liver. Unlike conventional T cells, which are stimulated by peptide antigens presented by MHC molecules, MAIT cells recognize metabolite antigens derived from an intermediate in the microbial biosynthesis of riboflavin. MAIT cells mediate protective immunity to infections by riboflavin‐producing microbes via the production of cytokines and cytotoxicity. The discovery of stimulating MAIT cell antigens allowed for the development of an analytical tool, the MR1 tetramer, that binds specifically to the MAIT T cell receptor (TCR) and is becoming the gold standard for identification of MAIT cells by flow cytometry. This article describes protocols to characterize the phenotype of human MAIT cells in blood and tissues by flow cytometry using fluorescently labeled human MR1 tetramers alongside antibodies specific for MAIT cell markers. © 2019 by John Wiley & Sons, Inc. The main protocols include: Basic Protocol 1: Determining the frequency and steady‐state surface phenotype of human MAIT cells Basic Protocol 2: Determining the activation phenotype of human MAIT cells in blood Basic Protocol 3: Characterizing MAIT cell TCRs using TCR‐positive reporter cell lines Alternate protocols are provided for determining the absolute number, transcription factor phenotype, and TCR usage of human MAIT cells; and determining activation phenotype by staining for intracellular markers, measuring secreted cytokines, and measuring fluorescent dye dilution due to proliferation. Additional methods are provided for determining the capacity of MAIT cells to produce cytokine independently of antigen using plate‐bound or bead‐immobilized CD3/CD28 stimulation; and determining the MR1‐Ag dependence of MAIT cell activation using MR1‐blocking antibody or competitive inhibition. For TCR‐positive reporter cell lines, methods are also provided for evaluating the MAIT TCR‐mediated MR1‐Ag response, determining the capacity of the reporter lines to produce cytokine independently of antigen, determining the MR1‐Ag dependence of the reporter lines, and evaluating the MR1‐Ag response of the reporter lines using IL‐2 secretion. Support Protocols describe the preparation of PBMCs from human blood, the preparation of single‐cell suspensions from tissue, the isolation of MAIT cells by FACS and MACS, cloning MAIT TCRα and β chain genes and MR1 genes for transduction, generating stably and transiently transfected cells lines, generating a stable MR1 knockout antigen‐presenting cell line, and generating monocyte‐derived dendritic cells.

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Activation of Human Mucosal-Associated Invariant T Cells Induces CD40L-Dependent Maturation of Monocyte-Derived and Primary Dendritic Cells

Cited by 91 publications

References 42 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

MAIT cell-mediated cytotoxicity: Roles in host defense and therapeutic potentials in infectious diseases and cancer

Characterization of Human Mucosal‐associated Invariant T (MAIT) Cells

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