Circulating mucosal-associated invariant T cell levels and their cytokine levels in healthy adults

Lee, O-Jin; Cho, Young-Nan; Kee, Seung‐Jung; Kim, Moon‐Ju; Jin, Hye-Mi; Lee, Sung-Ji; Park, Ki-Jeong; Kim, Tae‐Jong; Lee, Shin-Seok; Kwon, Yong Soo; Kim, Nacksung; Shin, Myung-Geun; Shin, Jong‐Hee; Suh, Soon Pal; Ryang, Dong‐Wook; Park, Yong-Wook

doi:10.1016/j.exger.2013.11.003

Cited by 100 publications

(99 citation statements)

References 26 publications

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“…Our results now confirm that MAIT cells are present also among colonic iEL. Circulating MAIT cell frequencies have been shown to decrease with increasing age, at least in healthy subjects (36,37), but we could not document such an effect in the colon from this middle-aged and elderly patient material. In contrast to our results of higher MAIT cell frequencies in males, one of the latter studies (36) found no sex difference in circulating MAIT cell frequencies at the ages 50 y and above.…”

Section: Discussioncontrasting

confidence: 42%

Human Mucosa-Associated Invariant T Cells Accumulate in Colon Adenocarcinomas but Produce Reduced Amounts of IFN-γ

Sundström

Ahlmanner

Akéus

et al. 2015

The Journal of Immunology

118

164

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Mucosa-associated invariant T (MAIT) cells are innate-like T cells with a conserved TCR α-chain recognizing bacterial metabolites presented on the invariant MHC-related 1 molecule. MAIT cells are present in intestinal tissues and liver, and they rapidly secrete IFN-γ and IL-17 in response to bacterial insult. In colon cancer, IL-17–driven inflammation promotes tumor progression, whereas IFN-γ production is essential for antitumor immunity. Thus, tumor-associated MAIT cells may affect antitumor immune responses by their secreted cytokines. However, the knowledge of MAIT cell presence and function in tumors is virtually absent. In this study, we determined the frequency, phenotype, and functional capacity of MAIT cells in colon adenocarcinomas and unaffected colon lamina propria. Flow cytometric analyses showed significant accumulation of MAIT cells in tumor tissue, irrespective of tumor stage or localization. Colonic MAIT cells displayed an activated memory phenotype and expression of chemokine receptors CCR6 and CCR9. Most MAIT cells in unaffected colon tissues produced IFN-γ, whereas only few produced IL-17. Colonic MAIT cells also produced TNF-α, IL-2, and granzyme B. In the tumors, significantly lower frequencies of IFN-γ–producing MAIT cells were seen, whereas there were no differences in the other cytokines analyzed, and in vitro studies showed that secreted factors from tumor tissue reduced IFN-γ production from MAIT cells. In conclusion, MAIT cells infiltrate colon tumors but their ability to produce IFN-γ is substantially reduced. We suggest that MAIT cells have the capacity to promote local immune responses to tumors, but factors in the tumor microenvironment act to reduce MAIT cell IFN-γ production.

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Section: Discussioncontrasting

confidence: 42%

Human Mucosa-Associated Invariant T Cells Accumulate in Colon Adenocarcinomas but Produce Reduced Amounts of IFN-γ

Sundström

Ahlmanner

Akéus

et al. 2015

The Journal of Immunology

118

164

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“…Failure of MAIT cells to produce IL-17 following exposure to E. coli fed APCs was also reported by Lepore and colleagues [44]. This may also be true for IL-4 as, although Lee et al found that IL-4 was expressed following exposure of MAITs from healthy control PBMCs to PMA/Ionomycin, other studies did not detect any expression of Th2 related cytokines from MAIT cells following stimulation with PMA/ Ionomycin or with anti-CD3 and anti-CD28 [45,46,50]. Further research will therefore be required to clarify some of the differences in cytokine expression reported.…”

Section: Cytokine and Chemokine Expression By Mait Cellsmentioning

confidence: 73%

“…Low numbers of DP and CD4 + MAIT cells have also been reported [12,43,46]. In healthy adults, circulating MAIT cells are in a hypoproliferative state [47,48].…”

Section: Characteristics Of Mait Cellsmentioning

confidence: 98%

“…By age two, adult levels of circulating MAIT cells were detected [45]. More recently Lee et al [46] characterized circulating MAIT cells in a large sample of 133 healthy adults and reported high variability in circulating MAIT cell numbers across subjects (0.19-21.7%). Although no significant differences in numbers between males and females were found there was a significant decrease in MAIT cell numbers in elderly subjects (n = 45, ages 61-92) versus young subjects (n = 44, ages [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40].…”

Section: Characteristics Of Mait Cellsmentioning

confidence: 99%

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Harnessing the antibacterial and immunological properties of mucosal-associated invariant T cells in the development of novel oral vaccines against enteric infections

Abautret-Daly¹,

Davitt²,

Lavelle³

2014

Biochemical Pharmacology

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“…13 MAIT cells comprise 1-10% of circulating CD3 + T cells in healthy adults. 14,15 Although their distribution in tissues has not been thoroughly investigated, they have been found to be enriched in the gastrointestinal tract, liver and airway. 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.…”

Section: What Are Mait Cells and What Is Known About Their Phenotype mentioning

confidence: 99%

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

2016

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SummaryMucosal-associated invariant T (MAIT) cells are donor-unrestricted lymphocytes that are surprisingly abundant in humans, representing 1-10% of circulating T cells and further enriched in mucosal tissues. MAIT cells recognize and are activated by small molecule ligands produced by microbes and presented by MR1, a highly conserved MHC-related antigen-presenting protein that is ubiquitously expressed in human cells. Increasing evidence suggests that MAIT cells play a protective role in anti-bacterial immunity at mucosal interfaces. Some fungi are known to produce MAIT-activating ligands, but the role of MAIT cells in fungal infections has not yet been investigated. In viral infections, specifically HIV, which has received the most study, MAIT cell biology is clearly altered, but the mechanisms explaining these alterations and their clinical significance are not yet understood. Many questions remain unanswered about the potential of MAIT cells for protection or pathogenesis in infectious diseases. Because they interact with the universal, donor-unrestricted ligand-presenting MR1 molecule, MAIT cells may be attractive immunotherapy or vaccine targets. New tools, including the development of MR1-ligand tetramers and next-generation T-cell receptor sequencing, have the potential to accelerate MAIT cell research and lead to new insights into the role of this unique set of lymphocytes in infectious diseases.

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Circulating mucosal-associated invariant T cell levels and their cytokine levels in healthy adults

Cited by 100 publications

References 26 publications

Human Mucosa-Associated Invariant T Cells Accumulate in Colon Adenocarcinomas but Produce Reduced Amounts of IFN-γ

Human Mucosa-Associated Invariant T Cells Accumulate in Colon Adenocarcinomas but Produce Reduced Amounts of IFN-γ

Harnessing the antibacterial and immunological properties of mucosal-associated invariant T cells in the development of novel oral vaccines against enteric infections

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

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