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. © 2010 Gold et al.
|Data di pubblicazione:||2010|
|Titolo:||Human mucosal associated invariant T cells detect bacterially infected cells|
|Autori:||Gold, Marielle C.; 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 B.; Harriff, Melanie J.; Lewinsohn, Deborah A.; Hansen, Ted H.; Lewinsohn, David M.|
|Digital Object Identifier (DOI):||10.1371/journal.pbio.1000407|
|Appare nelle tipologie:||Articolo su rivista|
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