12:00noon Monday 18th December
Room 208, 2nd floor,
Microbiology building,
720 Cumberland Street
Mucosal associated invariant T (MAIT) cells are an unconventional anti-bacterial T cell subset that are abundant in humans in blood, liver, and mucosal tissues. Unlike conventional T cells, MAIT cells express a semi-invariant T cell receptor (TCR) and like other unconventional T cells, MAIT cells express cytokine receptors, such as interleukin (IL)-12R and IL-18R, at high levels and can respond to cytokines, produced during bacterial or viral infections, independently of TCR stimulation. Activation via the two modes can occur independently or simultaneously, depending upon the stimuli. However, it is unclear whether the effector functions of human MAIT cells differ by mode of activation. We showed that TCR stimulation of both blood and liver derived MAIT cells triggered rapid acquisition of a polyfunctional proinflammatory phenotype, with the expression of multiple cytokines and chemokines, while the response to cytokine activation was slower and narrower. When the transcriptome of unstimulated blood and liver-derived MAIT cells were compared, there was no substantial difference in the circulatory and tissue residency gene expression signatures, suggesting that MAIT cells may recirculate between blood and liver. We further identified type I interferons as a major regulatory signal that can directly stimulate MAIT cells as well as enhancing the response of MAIT cells to TCR signals. Overall, this study has significantly advanced our knowledge of MAIT immunobiology.