Peripheral Blood Mucosal-Associated Invariant T Cells in Tuberculosis Patients and Healthy Mycobacterium tuberculosis-Exposed Controls

Abstract

In human blood, mucosal-associated invariant T (MAIT) cells are abundant T cells, which recognize antigens presented on non-polymorphic major histocompatibility complex-related 1 (MR1) molecules. MAIT cells are activated by mycobacteria, and prior human studies indicate that blood frequencies of MAIT cells, defined by cell surface markers, decline during TB disease, consistent with redistribution to the lungs. We tested whether frequencies of blood MAIT cells were altered in patients with TB disease relative to healthy Mycobacterium tuberculosis (Mtb)-exposed controls from Peru and South Africa. We quantified their frequencies using MR1 tetramers loaded with 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU). Unlike findings from prior studies, frequencies of blood MAIT cells were similar among TB-disease patients, latent and uninfected controls. In both cohorts, frequencies of MAIT cells defined by MR1-tetramer staining and co-expression 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 TB patients. MR1-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 roles in pathophysiology.