期刊
IMMUNOLOGY
卷 145, 期 3, 页码 443-453出版社
WILEY
DOI: 10.1111/imm.12461
关键词
bacteria; cell surface molecules; human; MHC; MR1 and MAIT cells; T cells
类别
资金
- National Institutes of Health (NIH) under the NIAID funded MIST Consortium [AI095776]
- National Institutes of Health (NIH) [T32AI007387]
- Burroughs Wellcome Fund/ASTMH Postdoctoral Fellowship in Tropical Infectious Diseases and Merit Review from the U.S. Department of Veterans Affairs Biomedical Laboratory Research and Development [I01 BX001231, I01 BX000533]
Mucosa-associated invariant T (MAIT) cells express the semi-invariant T-cell receptor TRAV1-2 and detect a range of bacteria and fungi through the MHC-like molecule MR1. However, knowledge of the function and phenotype of bacteria-reactive MR1-restricted TRAV1-2(+) MAIT cells from human blood is limited. We broadly characterized the function of MR1-restricted MAIT cells in response to bacteria-infected targets and defined a phenotypic panel to identify these cells in the circulation. We demonstrated that bacteria-reactive MR1-restricted T cells shared effector functions of cytolytic effector CD8(+) T cells. By analysing an extensive panel of phenotypic markers, we determined that CD26 and CD161 were most strongly associated with these T cells. Using FACS to sort phenotypically defined CD8(+) subsets we demonstrated that high expression of CD26 on CD8(+)TRAV1-2(+) cells identified with high specificity and sensitivity, bacteria-reactive MR1-restricted T cells from human blood. CD161(hi) was also specific for but lacked sensitivity in identifying all bacteria-reactive MR1-restricted T cells, some of which were CD161(dim). Using cell surface expression of CD8, TRAV1-2, and CD26(hi) in the absence of stimulation we confirm that bacteria-reactive T cells are lacking in the blood of individuals with active tuberculosis and are restored in the blood of individuals undergoing treatment for tuberculosis.
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