It is found on a broad range of lymphocytes, including CD4+, CD8+, + T-cells, and NK cells

It is found on a broad range of lymphocytes, including CD4+, CD8+, + T-cells, and NK cells. in elucidating MAIT cell restriction and function, and the role MAIT cells might play in the control of infection. infected cells. (1) Internalization of by an antigen-presenting cell, either through infection or actively by phagocytosis. (2) Lysis of the bacteria, within endocytic compartments, releases 5-A-RU, which is converted to 5-OE-RU or 5-OP-RU and binds to and stabilizes MR1. (3) The stable MR1 translocates to the cell surface, where it is presented along with other co-stimulatory molecules, e.g., CD80 or CD86. (4) Bacterial components trigger pathogen recognition receptors (PRR), such as TLR8. (5) PRR triggering drives cytokine expression, such as IL-12, and the activation of the inflammosome, resulting in the release of active-IL-18. (6) MAIT cells are activated either by TCR recognition of MR1 in combination with co-stimulatory receptors, e.g., CD28, and/or OT-R antagonist 2 OT-R antagonist 2 by cytokines, e.g., IL-12 and IL18. (7) Activated MAIT cells express pro-inflammatory cytokines, e.g., IFN, TNF, and IL-17. (8) These cytokines can directly act anti-bacterially, or recruit and stimulate other immune cells, e.g., neutrophils by IL-17. (9) Activation of MAIT cells upregulates perforin and granzyme B expression. (10) Theoretically, the degranulation of cytotoxic granules into infected cells (target cells), via recognition of MR1, could induce cell death and, thus, the potential clearance of infected cells. This review will explore what is currently known about MAIT cells in human beings. Comparisons between human and murine MAIT cells have been made elsewhere (4). Furthermore, we will discuss the role OT-R antagonist 2 that has played in identifying the functions of this cell type, and the potential role MAIT cells may have in controlling infections. MAIT Cell Phenotype In addition to possessing the V7.2-J33/12/20 TCR, MAIT cells can be identified in human OT-R antagonist 2 beings by the expression of a characteristic phenotypic signature composed of a number of additional surface and transcriptional markers. Memory phenotype In adults, MAIT cells typically express an effector memory phenotype: CD45RO+, CCR7?, CD62L?, CD27+, and CD28+ OT-R antagonist 2 (17C19). However, in cord blood, MAIT cells possess a na?ve phenotype (CD45RA+, CCR7+, CD62L+), but still retain a phenotypic signature characteristic of adult MAIT cells, including the expression of CD161, interleukin (IL)-18R, CD8, and CCR6 (3, 5, 17, 20). A recent study demonstrated that MAIT cells in the thymus, spleen, and mesenteric lymph nodes of aborted second trimester fetuses also had a Egfr na?ve phenotype and expressed only low levels of the characteristic MAIT cell markers, such as IL-18R and CD8, while MAIT cells in the fetal intestine, liver, and lung had a more memory phenotype (21). CD161 CD161 is a C-type lectin-like receptor originally identified by Lanier et al. (22). It is found on a broad range of lymphocytes, including CD4+, CD8+, + T-cells, and NK cells. The majority of NK cells express CD161 (>90%), while in the CD4+, CD8+, and + T-cell subsets, CD161 expression is limited to ~30% of cells (19, 23). However, within the CD8+ and CD8? CD4? T-cell population, CD161 expression can distinguish three separate subsets, CD161?, CD161intermediate/+, and CD161high/++; MAIT cells populate the CD161++ subset (17, 18). In adult peripheral blood, MAIT cells represent ~85% of the CD161++ subset (24). However, in cord blood, the MAIT cells make up a much smaller proportion of this subset, averaging ~15% of the CD161++ CD8+ T-cell population (21, 25, 26). During early childhood, this population expands so that by the age of 24?months the MAIT cell population already represents ~50% of the CD161++ CD8+ T-cell population (25). The function of CD161 on MAIT cells is yet to be fully elucidated. On NK cells, binding of CD161 to its ligand [lectin-like transcript (LLT) 1] leads to an inhibition of cytotoxicity (27C29). Two studies explored the role of CD161 on CD8+ T-cells and reached opposing conclusions (27, 29). Rosen et al. found that cross-linking CD161 had no effect on anti-CD3/CD28 stimulated CD8+T-cells in terms of IFN expression and inhibited TNF expression,.