Emerging features of MAIT cells and other unconventional T cell populations in human viral disease and vaccination

Abstract

MAIT cells are one representative of a group of related unconventional or pre-set T cells, and are particularly abundant in humans. While these unconventional T cell types, which also include populations of Vδ2 cells and iNKT cells, recognise quite distinct ligands, they share functional features including the ability to sense "danger" by integration of cytokine signals. Since such signals are common to many human pathologies, activation of MAIT cells in particular has been widely observed. In this review we will discuss recent trends in these data, for example the findings from patients with Covid-19 and responses to novel vaccines. Covid-19 is an example where MAIT cell activation has been correlated with disease severity by several groups, and the pathways leading to activation are being clarified, but the overall role of the cells in vivo requires further exploration. Given the potential wide functional responsiveness of these cells, which ranges from tissue repair to cytotoxicity, and likely impacts on the activity of many other cell populations, defining the role of these cells - not only as sensitive biomarkers but also as mediators - across human disease remains an important task.

Keywords: HIV; MAIT; SARS-COV2; Unconventional T cell; Viral infection.

Fig. 1

Differential infection kinetics impact on MAIT cells. In the context of acute infections (A), MAIT cells upregulate activation markers as the viral load increases but normalise in phenotype as soon as a robust adaptive immune response is mounted, and the viral infection is cleared. MAIT activation correlates with IFNα production and higher initial MAIT frequencies are correlated with fastened recovery overall implying a beneficial role of MAIT cells. In contrast, MAIT activation in protracted viral infections (B) is mainly driven by IL-18, appears to be long-lasting and is associated with more severe disease and worse clinical outcome. Figure was created with Biorender.com.