Human mucosal associated invariant T cells detect bacterially infected cells

Marielle C. Gold, Stefania Cerri, Susan Smyk-Pearson, Meghan E. Cansler, Todd M. Vogt, Jacob Delepine, Ervina Winata, Gwendolyn M. Swarbrick, Wei Jen Chua, Yik Y.L. Yu, Olivier Lantz, Matthew S. Cook, Megan D. Null, David B. Jacoby, Melanie J. Harriff, Deborah A. Lewinsohn, Ted H. Hansen, David M. Lewinsohn

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345 Scopus citations

Abstract

Control 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 Mtbuninfected individuals. Interestingly, these Mtb-reactive cells expressed the Va7.2 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.

Original languageEnglish (US)
JournalPLoS Biology
Volume8
Issue number6
DOIs
StatePublished - Jun 1 2010

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Gold, M. C., Cerri, S., Smyk-Pearson, S., Cansler, M. E., Vogt, T. M., Delepine, J., Winata, E., Swarbrick, G. M., Chua, W. J., Yu, Y. Y. L., Lantz, O., Cook, M. S., Null, M. D., Jacoby, D. B., Harriff, M. J., Lewinsohn, D. A., Hansen, T. H., & Lewinsohn, D. M. (2010). Human mucosal associated invariant T cells detect bacterially infected cells. PLoS Biology, 8(6). https://doi.org/10.1371/journal.pbio.1000407