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

doi:10.1371/journal.pbio.1000407

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

Research output: Contribution to journal › Article › peer-review

467 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 language	English (US)
Journal	PLoS Biology
Volume	8
Issue number	6
DOIs	https://doi.org/10.1371/journal.pbio.1000407
State	Published - Jun 2010

ASJC Scopus subject areas

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

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10.1371/journal.pbio.1000407

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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

Gold, MC, 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, DB , Harriff, MJ , Lewinsohn, DA, Hansen, TH & Lewinsohn, DM 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

@article{e4b915e156d24a8fb346a57836918aa1,

title = "Human mucosal associated invariant T cells detect bacterially infected cells",

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.",

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

note = "Funding Information: We thank Steven Truscott, Luiz Bermudez, Daved Fremont, and members of the Lewinsohn laboratories for helpful discussions, and Roger Croteau and Erin Merrifield for coordinating the human subjects research protocols. We thank Karen Dobos who has provided ongoing support in the characterization of the mycobacterial cell wall and is supported by NIH contract HHSN266200400091c. We thank Aurelie Snyder who is supported by NCRR/NIH S10-RR023432 and the OHSU MMI Imaging Core for her expert assistance in microscopy. We thank David Parker for his careful evaluation of the manuscript. We thank the Pacific Northwest Transplant Bank for their provision of lung tissue.",

year = "2010",

month = jun,

doi = "10.1371/journal.pbio.1000407",

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AU - Gold, Marielle C.

AU - Cerri, Stefania

AU - Smyk-Pearson, Susan

AU - Cansler, Meghan E.

AU - Vogt, Todd M.

AU - Delepine, Jacob

AU - Winata, Ervina

AU - Swarbrick, Gwendolyn M.

AU - Chua, Wei Jen

AU - Yu, Yik Y.L.

AU - Lantz, Olivier

AU - Cook, Matthew S.

AU - Null, Megan D.

AU - Jacoby, David B.

AU - Harriff, Melanie J.

AU - Lewinsohn, Deborah A.

AU - Hansen, Ted H.

AU - Lewinsohn, David M.

N1 - Funding Information: We thank Steven Truscott, Luiz Bermudez, Daved Fremont, and members of the Lewinsohn laboratories for helpful discussions, and Roger Croteau and Erin Merrifield for coordinating the human subjects research protocols. We thank Karen Dobos who has provided ongoing support in the characterization of the mycobacterial cell wall and is supported by NIH contract HHSN266200400091c. We thank Aurelie Snyder who is supported by NCRR/NIH S10-RR023432 and the OHSU MMI Imaging Core for her expert assistance in microscopy. We thank David Parker for his careful evaluation of the manuscript. We thank the Pacific Northwest Transplant Bank for their provision of lung tissue.

PY - 2010/6

Y1 - 2010/6

N2 - 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.

AB - 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.

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Human mucosal associated invariant T cells detect bacterially infected cells

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