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Human mucosal associated invariant T cells detect bacterially infected cells.

By Marielle Gold, Stefania Cerri, Susan Smyk-Pearson, Meghan Cansler, Todd Vogt, Jacob Delepine, Ervina Winata, Gwendolyn Swarbrick, Wei-Jen Chua, Yik Yu, Olivier Lantz, Matthew Cook, Megan Null, David Jacoby, Melanie Harriff, Deborah Lewinsohn, Ted Hansen and David Lewinsohn

Abstract

International audienceControl of infection with Mycobacterium tuberculosis (Mtb) requires Th1-type immunity, of which CD8+ T cells play a unique role. High frequency Mtb-reactive CD8+ T cells are present in both Mtb-infected and uninfected humans. We show by limiting dilution analysis that nonclassically restricted CD8+ T cells are universally present, but predominate in Mtb-uninfected individuals. Interestingly, these Mtb-reactive cells expressed the Valpha7.2 T-cell receptor (TCR), were restricted by the nonclassical MHC (HLA-Ib) molecule MR1, and were activated in a transporter associated with antigen processing and presentation (TAP) independent manner. These properties are all characteristics of mucosal associated invariant T cells (MAIT), an "innate" T-cell population of previously unknown function. These MAIT cells also detect cells infected with other bacteria. Direct ex vivo analysis demonstrates that Mtb-reactive MAIT cells are decreased in peripheral blood mononuclear cells (PBMCs) from individuals with active tuberculosis, are enriched in human lung, and respond to Mtb-infected MR1-expressing lung epithelial cells. Overall, these findings suggest a generalized role for MAIT cells in the detection of bacterially infected cells, and potentially in the control of bacterial infection

Topics: MESH: Amino Acid Sequence, MESH: CD8-Positive T-Lymphocytes, MESH: Receptors, Antigen, T-Cell, MESH: Clone Cells, MESH: Complementarity Determining Regions, MESH: Cross Reactions, MESH: HLA Antigens, MESH: Humans, MESH: Molecular Sequence Data, MESH: Mucous Membrane, MESH: Mycobacterium tuberculosis, [SDV.IMM]Life Sciences [q-bio]/Immunology
Publisher: 'Public Library of Science (PLoS)'
Year: 2010
DOI identifier: 10.1371/journal.pbio.1000407
OAI identifier: oai:HAL:inserm-00707307v1
Provided by: HAL-Inserm
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