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

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.

Quantitative and Qualitative Perturbations of CD8+ MAITs in Healthy Mycobacterium tuberculosis–Infected Individuals

“…Wong et al (17) found a trend toward decreased frequency of CD161 hi CD8 + T cells in PBMCs from LTBI compared with controls in a TB-endemic African setting. Other studies have found no difference in MAIT frequencies in LTBI compared with TB neg, or even an increase (16,18). These contradictory results may be explained by variations in M. tuberculosis exposure rates in endemic versus nonendemic TB areas, how well the latent infection is controlled, as well as a difference in how MAIT populations were defined.…”

“…One of the most frequent nonclassically restricted T cell populations in the blood are MR1-restricted T cells, which decrease in frequency in active TB (14,15). For LTBI, there have been contradicting results regarding the frequency of MAITs in PBMCs (14,(16)(17)(18). MR1-restricted T cells represent a significant fraction of CD8 + and CD4 -CD8 -T cells in peripheral blood (19,20).…”

Synthetic mycobacterial diacyl trehaloses reveal differential recognition by human T cell receptors and the C-type lectin Mincle

“…Next, we wanted to measure the frequency of DAT 2 -reactive T cells in a cohort of 150 human subjects 27 , 28 to determine if there is an Mtb infection or disease-associated expansion of DAT-specific T cells. PBMCs were isolated from 50 Peruvian individuals with active tuberculosis (TB) before the start of anti-TB drug treatment.…”

When it’s good to have MAITs

“…MAIT cells are multifaceted in their functional response to infections and in maintaining homeostasis, also contributing to tissue repair and wound healing 3 . In the context of M. tb , human blood MAIT cell frequencies are reportedly reduced during active infection, 4 suggestive of circulating MAIT cell migration into the tissues, although a recent large cohort study disputes this finding 5 . Human MAIT cells also secrete interferon‐gamma when cultured with M. tb ‐infected antigen‐presenting cells 4 .…”

“…3 In the context of M. tb, human blood MAIT cell frequencies are reportedly reduced during active infection, 4 suggestive of circulating MAIT cell migration into the tissues, although a recent large cohort study disputes this finding. 5 Human MAIT cells also secrete interferon-gamma when cultured with M. tb-infected antigen-presenting cells. 4 Similarly, in mice, MAIT T-cell receptor transgenic cells secrete interferongamma in response to BCG and can inhibit its intracellular growth.…”