Reconstitution of Circulating Mucosal-Associated Invariant T Cells after Allogeneic Hematopoietic Cell Transplantation: Its Association with the Riboflavin Synthetic Pathway of Gut Microbiota in Cord Blood Transplant Recipients

Konuma, Takaaki; Kohara, Chisato; Watanabe, Eri; Takahashi, Shunsuke; Ozawa, Genki; Suzuki, Kei; Mizukami, Motoko; Nagai, Etsuko; Jimbo, Koji; Kaito, Yuta; Isobe, Masamichi; Kato, Seiko; Takahashi, Satoshi; Chiba, Asako; Miyake, Sachiko; Tojo, Arinobu

doi:10.4049/jimmunol.1900681

Cited by 39 publications

(56 citation statements)

References 52 publications

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“…Recently it was demonstrated that the ability of microflora to support thymic development of MAIT cells was dependent on riboflavin biosynthesis, and that providing exogenous 5-OP-RU was sufficient to reconstitute MAIT cell development ( 71 ). Recent studies also demonstrate the importance of gut microbiota and the presence of rib genes, on MAIT cell reconstitution after allogenic haematopoietic cell transplantation in humans ( 72 , 73 ). Dysbiosis in viral infections or changes to the gut microbiota have been shown to be associated with impaired MAIT cell responses ( 74 ) and it is hypothesized that dysbiosis in metabolic conditions also affects MAIT cells, altering their capacity to promote barrier integrity, and instead triggering a pathogenic, inflammatory MAIT cell response ( 75 ).…”

Section: Mr1-antigen Recognition In Physiological Settingsmentioning

confidence: 98%

Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries

et al. 2020

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Mucosal-associated Invariant T (MAIT) cells recognize vitamin B-based antigens presented by the non-polymorphic MHC class I related-1 molecule (MR1). Both MAIT T cell receptors (TCR) and MR1 are highly conserved among mammals, suggesting an important, and conserved, immune function. For many years, the antigens they recognize were unknown. The discovery that MR1 presents vitamin B-based small molecule ligands resulted in a rapid expansion of research in this area, which has yielded information on the role of MAIT cells in immune protection, autoimmune disease and recently in homeostasis and cancer. More recently, we have begun to appreciate the diverse nature of the small molecule ligands that can bind MR1, with several less potent antigens and small molecule drugs that can bind MR1 being identified. Complementary structural information has revealed the complex nature of interactions defining antigen recognition. Additionally, we now view MAIT cells (defined here as MR1-riboflavin-Ag reactive, TRAV1-2 + cells) as one subset of a broader family of MR1-reactive T cells (MR1T cells). Despite these advances, we still lack a complete understanding of how MR1 ligands are generated, presented and recognized in vivo . The biological relevance of these MR1 ligands and the function of MR1T cells in infection and disease warrants further investigation with new tools and approaches.

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Section: Mr1-antigen Recognition In Physiological Settingsmentioning

confidence: 98%

Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries

et al. 2020

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“…They are innate-like T cells that highly express CD161 and a semi-invariant αβ TCRs that recognize microbial metabolites presented by MR1 [89]. MAIT cells can be activated in MR1-dependent and MR1-independent ways, although expansion requires circulating B cells and commensal microbiota [89][90][91][92]. In the allo-HCT setting, no associations between high MAIT cell numbers and protection from infections have been reported so far [93].…”

Section: Mait Cellsmentioning

confidence: 99%

“…In the allo-HCT setting, no associations between high MAIT cell numbers and protection from infections have been reported so far [93]. However, low frequencies of MAIT cells in the graft and post-HCT are associated with severe GvHD [74,[92][93][94][95], and higher numbers seem to be associated with improved overall survival [94].…”

Section: Mait Cellsmentioning

confidence: 99%

“…Reconstitution of MAIT cells post-HCT significantly correlates with age [92,94] and cell source [92,93,96,97]. Early MAIT cell reconstitution is driven by the HPE of the MAIT cells transferred with the graft [93].…”

Section: Mait Cellsmentioning

confidence: 99%

“…Since CB contains much lower frequencies of MAIT cells compared with adult graft sources [97], their reconstitution is highly impaired following CBT [93,96]. Extremely low counts remain up to 12 months [92,96], and normal values after CBT are only reached around 5 years in children [96] and around 10 years in adults [92]. On the contrary, a rapid recovery to a plateau can be seen from Day 30 to Day 100 post-BMT/PBT [93].…”

Section: Mait Cellsmentioning

confidence: 99%

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Reconstitution of T Cell Subsets Following Allogeneic Hematopoietic Cell Transplantation

Dekker

Koning

Lindemans

et al. 2020

Cancers

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Allogeneic (allo) hematopoietic cell transplantation (HCT) is the only curative treatment option for patients suffering from chemotherapy-refractory or relapsed hematological malignancies. The occurrence of morbidity and mortality after allo-HCT is still high. This is partly correlated with the immunological recovery of the T cell subsets, of which the dynamics and relations to complications are still poorly understood. Detailed information on T cell subset recovery is crucial to provide tools for better prediction and modulation of adverse events. Here, we review the current knowledge regarding CD4+ and CD8+ T cells, γδ T cells, iNKT cells, Treg cells, MAIT cells and naive and memory T cell reconstitution, as well as their relations to outcome, considering different cell sources and immunosuppressive therapies. We conclude that the T cell subsets reconstitute in different ways and are associated with distinct adverse and beneficial events; however, adequate reconstitution of all the subsets is associated with better overall survival. Although the exact mechanisms involved in the reconstitution of each T cell subset and their associations with allo-HCT outcome need to be further elucidated, the data and suggestions presented here point towards the development of individualized approaches to improve their reconstitution. This includes the modulation of immunotherapeutic interventions based on more detailed immune monitoring, aiming to improve overall survival changes.

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MAIT cells and their implication in human oral diseases

et al. 2022

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Reconstitution of Circulating Mucosal-Associated Invariant T Cells after Allogeneic Hematopoietic Cell Transplantation: Its Association with the Riboflavin Synthetic Pathway of Gut Microbiota in Cord Blood Transplant Recipients

Abstract: This information is current as RecipientsMicrobiota in Cord Blood Transplant Riboflavin Synthetic Pathway of Gut Transplantation: Its Association with the Allogeneic Hematopoietic Cell Mucosal-Associated Invariant T Cells after Reconstitution of Circulating

Cited by 39 publications

References 52 publications

Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries

Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries

Reconstitution of T Cell Subsets Following Allogeneic Hematopoietic Cell Transplantation

MAIT cells and their implication in human oral diseases

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