High expression of CD26 accurately identifies human bacteria‐reactive MR1‐restricted MAIT cells. Issue 3 (29th March 2015)

• Record Type: Journal Article
• Authors: Sharma, Prabhat K.; Wong, Emily B.; Napier, Ruth J.; Bishai, William R.; Ndung'u, Thumbi; Kasprowicz, Victoria O.; Lewinsohn, Deborah A.; Lewinsohn, David M.; Gold, Marielle C.
• Is Part Of: Immunology. Volume 145:Issue 3(2015:Jul.)
• Page Start: 443
• Page End: 453
• Publication Date: 2015-03-29
• Subjects: Immunology -- Periodicals
• DOI: 10.1111/imm.12461
• Languages: English
• ISSNs: 0019-2805

Abstract

<abstract abstract-type="main" id="imm12461-abs-0001"> <title>Summary</title> <p>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<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> subsets we demonstrated that high expression of CD26 on CD8<sup>+</sup> TRAV1–2<sup>+</sup> cells identified with high specificity and sensitivity, bacteria‐reactive MR1‐restricted T cells from human blood. CD161<sup>hi</sup> was also specific for but lacked sensitivity in identifying all bacteria‐reactive MR1‐restricted T cells, some of which were CD161<sup>dim</sup>. Using cell surface expression of CD8, TRAV1–2, and CD26<sup>hi</sup> 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.</p> </abstract>