Ontogeny of MAIT Cells in Neonates and Hematopoietic Stem Cell Transplant Recipients

NCT ID: NCT02403089

Last Updated: 2023-02-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

300 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-03-31

Study Completion Date

2018-02-28

Brief Summary

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The objective of this study is 1/ to determine the rate and kinetics of MAIT cell expansion and maturation in neonates in relation with gestational age, and in HSCT recipient children in relation with the source of donor stem cells, 2/ to correlate gut microbiota diversity and function with MAIT cell maturation and function in neonates and HSCT recipients; and 3/ to link MAIT cells and gut microbiota composition with microbial infections and severe intestinal inflammatory events in term and preterm neonates, and in HSCT recipients

Detailed Description

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The mucosa-associated invariant T (MAIT) cells are innate-like T cells with restricted T cell receptor (TCR) usage, which are preferentially localized in mucosal tissues and respond to microbial infection by rapidly producing cytokines and cytotoxic effectors. They recognize the non-classical related molecule (MR1). MAIT cells react against a newly identified class of antigens presented by MR1: Riboflavin (Rib) precursors, which are found in most bacteria and yeasts. Currently, very little is known about the ontogeny of MAIT cells in the human, because of the difficulty to follow longitudinally their development. Cross-sectional studies have identified only the initial (cord blood) and final (adult subjects) steps of human MAIT cell maturation program. Moreover, there are no data on relationships between human MAIT cell expansion and maturation, and gut microbiota development. Given the potential importance of MAIT cells in protection from microbial infections at epithelial surfaces, we will investigate the maturation dynamics of MAIT cells in relation with gut microbiota diversity and function in two clinical settings characterized by a high predisposition to severe microbial infections before the establishment of protective adaptive immunity, namely i/ the neonatal period and ii/ the early immune reconstitution period following allogeneic hematopoietic stem cell transplantation (HSCT) in children. Our study will combine multiparametric phenotypic and functional characterization of MAIT cells with the use of new molecular microbiota analytic methodology (high throughput sequencing, metagenomics, Rib microbiology) to determine how the presence or functionality of MAIT cells is influenced by the gut microbiota.

Our consortium is composed of three independent research teams, experts in innate immunity, microbial ecology and MAIT cell biology, three independent clinical teams providing exceptional resources to patient samples, and one team providing expertise for methodology and statistical analysis. Their synergistic interaction will offer the various complementary expertise that is necessary for this project.

This project will decipher how MAIT cell numbers or functions are influenced by the gut microbiota composition, and reciprocally, how MAIT cells regulate or control expansion of gut microbiota components competing with opportunistic or pathogenic bacteria or responsible for infections. Ultimately, this study will determine how and when gut microbiota and MAIT cell interactions are involved in the control of severe infectious or intestinal inflammatory events in high risk infants, an indispensable step to design predictive biomarkers and ultimately propose new therapeutic options.

Conditions

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Term and Preterm Neonates (24-41 Weeks Gestational Age) Hematopoietic Stem Cell Transplant Recipient Children

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

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neonates

neonates 24-41 weeks gestational age

Tubes fund recovery blood count

Intervention Type OTHER

Tubes fund recovery of blood counts among newborns

children

hematopoietic stem cell transplant recipient children (\< 18 years old, donor source: cord blood or genoidentical donor)

the rest of the blood test and stool sample

Intervention Type OTHER

blood samples on the recovery kinetics after transplant. The rest of the blood test and stool sample done as part of a routine examination.

Interventions

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Tubes fund recovery blood count

Tubes fund recovery of blood counts among newborns

Intervention Type OTHER

the rest of the blood test and stool sample

blood samples on the recovery kinetics after transplant. The rest of the blood test and stool sample done as part of a routine examination.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* neonates 24-41 weeks gestational age
* hematopoietic stem cell transplant recipient children (\< 18 years old, donor source: cord blood or genoidentical donor)

Exclusion Criteria

* neonates : chromosomal abnormalities detected before birth
* source of HSCT: phenol-identical donors
Minimum Eligible Age

1 Day

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role collaborator

Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement

OTHER

Sponsor Role collaborator

Institut Curie

OTHER

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Biran Valérie, PHD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

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Hôpital Robert Debré

Paris, , France

Site Status

Countries

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France

References

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Ben Youssef G, Tourret M, Salou M, Ghazarian L, Houdouin V, Mondot S, Mburu Y, Lambert M, Azarnoush S, Diana JS, Virlouvet AL, Peuchmaur M, Schmitz T, Dalle JH, Lantz O, Biran V, Caillat-Zucman S. Ontogeny of human mucosal-associated invariant T cells and related T cell subsets. J Exp Med. 2018 Feb 5;215(2):459-479. doi: 10.1084/jem.20171739. Epub 2018 Jan 16.

Reference Type RESULT
PMID: 29339446 (View on PubMed)

Tourret M, Talvard-Balland N, Lambert M, Ben Youssef G, Chevalier MF, Bohineust A, Yvorra T, Morin F, Azarnoush S, Lantz O, Dalle JH, Caillat-Zucman S. Human MAIT cells are devoid of alloreactive potential: prompting their use as universal cells for adoptive immune therapy. J Immunother Cancer. 2021 Oct;9(10):e003123. doi: 10.1136/jitc-2021-003123.

Reference Type DERIVED
PMID: 34615705 (View on PubMed)

Other Identifiers

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NI14006

Identifier Type: -

Identifier Source: org_study_id

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