Ontogeny of MAIT Cells in Neonates and Hematopoietic Stem Cell Transplant Recipients
Condition: Term and Preterm Neonates (24-41 Weeks Gestational Age); Hematopoietic Stem Cell Transplant Recipient Children
MeSH terms: Premature Birth
Study type: Observational

Summary: 
      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: 
      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.
    

Intervention name(s): Tubes fund recovery blood count; the rest of the blood test and stool sample
Intervention type(s): Other; Other
Intervention description(s): Tubes fund recovery of blood counts among newborns; blood samples on the recovery kinetics after transplant. The rest of the blood test and stool sample done as part of a routine examination.
Observational model: Other
Time perspective: Prospective
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
      
Biospecimen description: 
      funds tubes samples taken as part of routine care for newborns and in allograft recipients
      children will be recovered. Mononuclear cells from cord blood will be isolated and stored in
      liquid nitrogen in the laboratory of Immunology before achieving functional tests.

      • Rectal swabs and gastric aspirates aliquots made as part of routine care for newborns, and
      rectal swabs made as part of routine care in HSCT allograft recipients, will be stored at -80
      ° C in the laboratory of Immunology.
    
Keywords: MAIT (Mucosal-Associated Invariant T) cells; Gut microbiota; Preterm birth; Hematopoietic stem cell transplantation; Microbial infections