Role of non-canonical T cells in homeostasis and pathology

Abstract

In addition to the subsets of T lymphocytes and innate lymphocytes (innate lymphoid cells), the well-known players in adaptive immunity, there is an intermediate group of lymphocytes (innate-like cells) that already possess the T cell receptor, but with a restricted repertoire. This group includes γδT cells, subsets of type I and II NKT cells carrying both T cell receptor and NK-cell receptors, and mucosal-associated invariant T (MAIT) cells. The development of innate-like cells occurs in the thymus, but their positive and negative selection takes place without the participation of thymic epithelial cells. A distinctive feature is that innate-like cells acquire an effector phenotype already in the thymus, and therefore do not require complex activation reactions during antigen recognition. Upon exit from the thymus, noncanonical T cells express chemokine receptors, allowing them to migrate into barrier tissues at an early age. A characteristic feature of the T cell receptor innate-like cells is the recognition of non-peptide antigens presented in non-polymorphic histocompatibility molecules (MHC-Ib). This type of molecule includes the CD1 a/b/c/d/e molecule and the MR1 molecule. These molecules present lipid, glycolipid antigens and metabolites of B vitamins, synthesized by various representatives of the microbiota. The presence of functionally different subpopulations of innate-like cells with an activated phenotype allows them to quickly respond to the antigen by producing cytokines typical of Th1, Th2, Th17. They also exhibit cytotoxic and immunoregulatory activity. These cells are actively involved in regulation of barrier tissue homeostasis and interaction with microbiota. They synthesize growth factors for epithelial cells, fibroblasts, and vascular endothelium, which are required for regeneration of damaged tissues. They also participate in anti-infectious defense, directing the development of the immune response. Moreover, they have been found to be involved in many autoimmune diseases. The special functions of innate-like cells make them a promising target for therapeutic interventions. It has been shown that antibiotics, salicylates and some other well-known drugs exert certain effects on the innate-like cells. Different dietary options also affect the activity of these cells.