Tim-3 expression is induced by mycobacterial antigens and identifies tissue-resident subsets of MAIT cells from patients with tuberculosis.

Tissue-resident MAIT cells in tuberculous pleural effusions, the site of tuberculosis infection, were investigated in the study. Tim-3+CD69+CD103+ and CD39+CD69+CD103+ tissue-resident MAIT cell subsets were identified in tuberculous pleural effusions. Tim-3 expression in MAIT cells was greatly induced and CD39 expression was elevated following ex vivo stimulation with Mycobacterium tuberculosis antigens. Mycobacterial antigen-stimulated Tim-3+CD69+CD103+ tissue-resident MAIT cells had higher frequency of IFN-γ- and granzyme B-producing cells than Tim-3-CD69+CD103+ subset, while CD39+CD69+CD103+ MAIT cells had similar frequency of IFN-γ-positive cells but higher ratio of granzyme B-producing cells than CD39-CD69+CD103+ subset. Blocking of IL-2, IL-12p70 or IL-18 but not IL-15 led to significantly reduced expression of Tim-3 compared with isotype antibody control. In contrast, CD39 expression was not influenced by any of the cytokines tested. Tim-3+ MAIT cells had higher levels of lipid uptake and lipid content than Tim-3- cells. It is concluded that Tim-3+CD69+CD103+ tissue-resident MAIT cells were elevated in tuberculous pleural effusions and had higher capacity to produce effector molecules of IFN-γ and granzyme B.