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

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

Study Overview

• Status: Completed
• Conditions: Term and Preterm Neonates (24-41 Weeks Gestational Age); Hematopoietic Stem Cell Transplant Recipient Children
• Intervention / Treatment: Other: Tubes fund recovery blood count; Other: the rest of the blood test and stool sample

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• France
  • Paris, France, 75019
    • Hôpital Robert Debré

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

newborns hospitalized in the Neonatal Intensive Care Unit of the Hospital Robert Debré and grafted children hospitalized in the Hematology-Immunology Pediatric Service of the Hospital Robert Debré

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
neonates; neonates 24-41 weeks gestational age	Other: Tubes fund recovery blood count; 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)	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MAIT cell numbering neonates after birth	Absolute number, percentage and phenotype of MAIT cells by flow cytometry in the circulating blood after birth according to gestational age and / or maternal-fetal infections (IMF), or after allogeneic HSCT according to the origin of HSCs.	to 60days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute number of MAIT	Absolute number and percentage of MAIT among mothers of infants on the day of delivery and in geno-identical donors before transplantation.	to 60days
Absolute number of other immune cell populations	Absolute number and percentage of other immune cell populations by flow cytometry on the same blood samples.	to 60 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; Institut Curie; Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
• Investigators: Principal Investigator: Biran Valérie, PHD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): February 1, 2018

Study Registration Dates

• First Submitted: March 6, 2015
• First Submitted That Met QC Criteria: March 25, 2015
• First Posted (Estimate): March 31, 2015

Study Record Updates

• Last Update Posted (Actual): February 3, 2023
• Last Update Submitted That Met QC Criteria: February 2, 2023
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Gut microbiota; Hematopoietic stem cell transplantation; Preterm birth; MAIT (Mucosal-Associated Invariant T) cells; Microbial infections
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: NI14006