Development of mucosal‐associated invariant T cells

Abstract

Mucosal-associated invariant T (MAIT) cells develop in the thymus and migrate into the periphery to become the largest antigen-specific αβ T-cell population in the human immune system. However, the frequency of MAIT cells varies widely between human individuals, and the basis for this is unclear. While MAIT cells are highly conserved through evolution and are phenotypically similar between humans and mice, they represent a much smaller proportion of total T cells in mice. In this review, we discuss how MAIT cells transition through a three-stage development pathway in both mouse and human thymus, and continue to mature and expand after they leave the thymus. Moreover, we will explore and speculate on how specific factors regulate different stages of this process.

MAIT cells: the end of the beginning?

“…2,3 The development of this cell type and its selection in the thymus is next explored, an area that can give insight into not only MAIT cell biology but that of other related cell types. 4 The last three reviews look further into the biological roles of these cells. This includes a perspective on the best-described areas of MAIT cell researchnamely antimicrobial defense, based on the specificity of the TCR for the microbially-derived ligand.…”

“…This leads naturally on from the cells themselves to what they recognize – a major set of discoveries which has led to an explosion of interest in the field . The development of this cell type and its selection in the thymus is next explored, an area that can give insight into not only MAIT cell biology but that of other related cell types . The last three reviews look further into the biological roles of these cells.…”

MicroRNA‐managing the development of MAIT cells

“…This included developmental studies that revealed a three‐step maturation pathway in humans and mice. In mice, these steps are defined as immature stage 1 (CD24 + CD44 − ), intermediate stage 2 (CD24 − CD44 − ) and mature stage 3 (CD24 − CD44 + ) MAIT cells (Figure ) . One factor that was found to be essential for MAIT cell development was the enzyme Drosha .…”

“…The study by Winter and colleagues adds to growing number of studies elucidating how MAIT cell development is regulated, and offers another checkpoint control factor that regulates this important population of T cells. As miR‐181s are conserved between mice and humans, this study raises the question of whether these regulators also control human MAIT cell development and/or post‐thymic maturation and expansion.…”

“…In mice, these steps are defined as immature stage 1 (CD24 + CD44 À ), intermediate stage 2 (CD24 À CD44 À ) and mature stage 3 (CD24 À CD44 + ) MAIT cells ( Figure 1). 8,9 One factor that was found to be essential for MAIT cell development was the enzyme Drosha. 8 Drosha, along with Dicer, are RNAseIII enzymes responsible for the generation of canonical mature micro-RNAs (miRs).…”