Mucosal-associated invariant T (MAIT) cells are a population of innate-like lymphocytes within the gut, liver and blood, expressing a semi-invariant T cell receptor (TCR) and high levels of the C-type lectin-like receptor, CD161. These cells recognise a metabolite of the microbial riboflavin synthesis pathway, presented by the highly conserved Major Histocompatibility Complex (MHC) class I-related protein, MR1, and are critical for the control of bacterial infections. The factors regulating the broad effector functions of MAIT cells have not been fully investigated. Utilising a novel flow cytometric killing assay, MAIT cells were shown here to require the induction of a cytotoxic phenotype through bacterial stimulation to efficiently kill target cells. Further in depth phenotypic analysis highlighted a distinct non-cytotoxic subset of CD4+ MAIT cells, with an altered cytokine-producing capacity, enriched within lymphoid tissues. Investigation into the potential role of these cells in psoriatic diseases revealed that MAIT cells within the synovial fluid of psoriatic arthritis patients are potently activated with increased IL-17 production, their frequency correlating with measures of clinical activity. MAIT cells also have an innate-like responsiveness to cytokines, a feature originally attributed to Natural Killer (NK) cells. Microarray analysis and mass cytometry experiments demonstrated that CD161 marks immature NK cells that have retained this ability to respond to innate cytokines during their differentiation, and is lost upon cytomegalovirus (CMV)-induced maturation in both healthy and human immunodeficiency virus (HIV)-infected patients. Thus, CD161 marks cells with innate-effector functions both in T cells and NK cells.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:730591 |
| Date | January 2015 |
| Creators | Kurioka, Ayako |
| Contributors | Klenerman, Paul |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://ora.ox.ac.uk/objects/uuid:f994e661-d241-4a1c-ac56-b6bea73346ac |
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