Human mucosal associated invariant T cells detect bacterially infected cells

Marielle 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 Jacoby, Melanie Harriff, Deborah Lewinsohn, Ted H. Hansen, David Lewinsohn

Research output: Contribution to journalArticle

318 Citations (Scopus)

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 2010

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T-cells
Mycobacterium tuberculosis
T-lymphocytes
T-Lymphocytes
cells
Lung
Antigen Presentation
Infection Control
T-Cell Antigen Receptor
lungs
Bacterial Infections
Mucosal-Associated Invariant T Cells
Immunity
Blood Cells
Tuberculosis
Epithelial Cells
mononuclear leukocytes
Dilution
bacterial infections
Bacteria

ASJC Scopus subject areas

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

Cite this

Human mucosal associated invariant T cells detect bacterially infected cells. / Gold, Marielle; Cerri, Stefania; Smyk-Pearson, Susan; Cansler, Meghan E.; Vogt, Todd M.; Delepine, Jacob; Winata, Ervina; Swarbrick, Gwendolyn M.; Chua, Wei Jen; Yu, Yik Y L; Lantz, Olivier; Cook, Matthew S.; Null, Megan D.; Jacoby, David; Harriff, Melanie; Lewinsohn, Deborah; Hansen, Ted H.; Lewinsohn, David.

In: PLoS Biology, Vol. 8, No. 6, 06.2010.

Research output: Contribution to journalArticle

Gold, M, Cerri, S, Smyk-Pearson, S, Cansler, ME, Vogt, TM, Delepine, J, Winata, E, Swarbrick, GM, Chua, WJ, Yu, YYL, Lantz, O, Cook, MS, Null, MD, Jacoby, D, Harriff, M, Lewinsohn, D, Hansen, TH & Lewinsohn, D 2010, 'Human mucosal associated invariant T cells detect bacterially infected cells', PLoS Biology, vol. 8, no. 6. https://doi.org/10.1371/journal.pbio.1000407
Gold M, Cerri S, Smyk-Pearson S, Cansler ME, Vogt TM, Delepine J et al. Human mucosal associated invariant T cells detect bacterially infected cells. PLoS Biology. 2010 Jun;8(6). https://doi.org/10.1371/journal.pbio.1000407
Gold, Marielle ; Cerri, Stefania ; Smyk-Pearson, Susan ; Cansler, Meghan E. ; Vogt, Todd M. ; Delepine, Jacob ; Winata, Ervina ; Swarbrick, Gwendolyn M. ; Chua, Wei Jen ; Yu, Yik Y L ; Lantz, Olivier ; Cook, Matthew S. ; Null, Megan D. ; Jacoby, David ; Harriff, Melanie ; Lewinsohn, Deborah ; Hansen, Ted H. ; Lewinsohn, David. / Human mucosal associated invariant T cells detect bacterially infected cells. In: PLoS Biology. 2010 ; Vol. 8, No. 6.
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