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Cited by 598

The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.

Stepwise Development of MAIT Cells in Mouse and Human

Open access
Martin, Emmanuel, Treiner, Emmanuel, Duban, Livine, Guerri, Lucia, Laude, Hélène, Toly, Cécile, Premel, Virginie, Devys, Anne, Moura, Ivan C, Tilloy, Florence, Cherif, Stéphane, Vera, Gabriella, Latour, Sylvain, Soudais, Claire, Lantz, Olivier·2009·PLoS Biology
DOI 10.1371/journal.pbio.1000054
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Abstract

Mucosal-associated invariant T (MAIT) cells display two evolutionarily conserved features: an invariant T cell receptor (TCR)alpha (iTCRalpha) chain and restriction by the nonpolymorphic class Ib major histocompatibility complex (MHC) molecule, MHC-related molecule 1 (MR1). MR1 expression on thymus epithelial cells is not necessary for MAIT cell development but their accumulation in the gut requires MR1 expressing B cells and commensal flora. MAIT cell development is poorly known, as these cells have not been found in the thymus so far. Herein, complementary human and mouse experiments using an anti-humanValpha7.2 antibody and MAIT cell-specific iTCRalpha and TCRbeta transgenic mice in different genetic backgrounds show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. Mouse MAIT cells are selected in an MR1-dependent manner both in fetal thymic organ culture and in double iTCRalpha and TCRbeta transgenic RAG knockout mice. In the latter mice, MAIT cells do not expand in the periphery unless B cells are added back by adoptive transfer, showing that B cells are not required for the initial thymic selection step but for the peripheral accumulation. In humans, contrary to natural killer T (NKT) cells, MAIT cells display a naïve phenotype in the thymus as well as in cord blood where they are in low numbers. After birth, MAIT cells acquire a memory phenotype and expand dramatically, up to 1%-4% of blood T cells. Finally, in contrast with NKT cells, human MAIT cell development is independent of the molecular adaptor SAP. Interestingly, mouse MAIT cells display a naïve phenotype and do not express the ZBTB16 transcription factor, which, in contrast, is expressed by NKT cells and the memory human MAIT cells found in the periphery after birth. In conclusion, MAIT cells are selected by MR1 in the thymus on a non-B non-T hematopoietic cell, and acquire a memory phenotype and expand in the periphery in a process dependent both upon B cells and the bacterial flora. Thus, their development follows a unique pattern at the crossroad of NKT and gammadelta T cells.

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Crossref · 10.1371/journal.pbio.1000054

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Metadata

Authors
Martin, E., Treiner, E., Duban, L., Guerri, L., Laude, H., Toly, C., Premel, V., Devys, A., Moura, I. C., Tilloy, F., Cherif, S., Vera, G., Latour, S., Soudais, C., & Lantz, O.
Venue
PLoS Biology
Publisher
Public Library of Science (PLoS)
Published
2009-03-10
Volume
7
Issue
3
Pages
e1000054
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
DOI
10.1371/journal.pbio.1000054
OpenAlex
W1981700081
Cited by
598
References
38
FWCI
6.24
Type
journal article
Language
en
Open access
gold

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