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Peripheral blood mucosal-associated invariant T Cells in tuberculosis patients and healthy mycobacterium tuberculosis-exposed controls

Suliman, Sara, Gela, Anele, Mendelsohn, Simon C., Iwany, Sarah K., Tamara, Kattya Lopez, Mabwe, Simbarashe, Bilek, Nicole, Darboe, Fatoumatta, Fisher, Michelle, Corbett, Alexandra J., Kjer-Nielsen, Lars, Eckle, Sidonia B. G., Huang, Chuan-Chin, Zhang, Zibiao, Lewinsohn, David M., McCluskey, James, Rossjohn, Jamie, Hatherill, Mark, León, Segundo R., Calderon, Roger I., Lecca, Leonid, Murray, Megan, Scriba, Thomas J., Van Rhijn, Ildiko and Moody, D. Branch 2020. Peripheral blood mucosal-associated invariant T Cells in tuberculosis patients and healthy mycobacterium tuberculosis-exposed controls. Journal of Infectious Diseases 222 (6) , pp. 995-1007. 10.1093/infdis/jiaa173

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Abstract

Background In human blood, mucosal-associated invariant T (MAIT) cells are abundant T cells that recognize antigens presented on non-polymorphic major histocompatibility complex-related 1 (MR1) molecules. The MAIT cells are activated by mycobacteria, and prior human studies indicate that blood frequencies of MAIT cells, defined by cell surface markers, decline during tuberculosis (TB) disease, consistent with redistribution to the lungs. Methods We tested whether frequencies of blood MAIT cells were altered in patients with TB disease relative to healthy Mycobacterium tuberculosis-exposed controls from Peru and South Africa. We quantified their frequencies using MR1 tetramers loaded with 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil. Results Unlike findings from prior studies, frequencies of blood MAIT cells were similar among patients with TB disease and latent and uninfected controls. In both cohorts, frequencies of MAIT cells defined by MR1-tetramer staining and coexpression of CD161 and the T-cell receptor alpha variable gene TRAV1-2 were strongly correlated. Disease severity captured by body mass index or TB disease transcriptional signatures did not correlate with MAIT cell frequencies in patients with TB. Conclusions Major histocompatibility complex (MHC)-related 1-restrictied MAIT cells are detected at similar levels with tetramers or surface markers. Unlike MHC-restricted T cells, blood frequencies of MAIT cells are poor correlates of TB disease but may play a role in pathophysiology.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: University of Chicago Press / Oxford University Press (OUP): Policy A1 - Oxford Open Option C
ISSN: 0022-1899
Date of Acceptance: 6 April 2020
Last Modified: 09 Sep 2020 13:50
URI: http://orca.cf.ac.uk/id/eprint/132919

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