Destined for the intestine: thymic selection of TCRαβ CD8αα intestinal intraepithelial lymphocytes

Abstract

The immune system is composed of a variety of different T cell lineages distributed through both secondary lymphoid tissue and non-lymphoid tissue. The intestinal epithelium is a critical barrier surface that contains numerous intraepithelial lymphocytes that aid in maintaining homeostasis at that barrier. This review focuses on T Cell Receptor αβ (TCRαβ) CD8αα intraepithelial lymphocytes, and how recent advances in the field clarify how this unique T cell subset is selected, matures, and functions in the intestines. We consider how the available evidence reveals a story of ontogeny starting from agonist selection of T cells in the thymus and finishing through the specific signaling environment of the intestinal epithelium. We conclude with how this story raises further key questions about the development of different ontogenic waves of TCRαβ CD8αα IEL and their importance for intestinal epithelial homeostasis.

Characterization of Bovine Intraepithelial T Lymphocytes in the Gut

“…T-IELs are categorized into two groups based on their origin: natural and induced [ 79 ]. Natural T-IELs comprise the TCRαβ + CD8αα + and TCRγδ + subsets, both of which exhibit innate-like features [ 22 , 42 , 61 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ]. After encountering endogenous self-antigens through their TCR in the thymus or extrathymic organs, these natural T-IELs rapidly populate the T-IEL compartment [ 22 , 80 , 87 , 88 , 89 , 90 ].…”

“…Natural T-IELs comprise the TCRαβ + CD8αα + and TCRγδ + subsets, both of which exhibit innate-like features [ 22 , 42 , 61 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ]. After encountering endogenous self-antigens through their TCR in the thymus or extrathymic organs, these natural T-IELs rapidly populate the T-IEL compartment [ 22 , 80 , 87 , 88 , 89 , 90 ]. Despite the fact that the potential extrathymic origin of the TCRαβ + CD8αα + subset remains a topic of debate, it has been generally accepted that they originate in the thymus [ 22 , 42 , 80 , 87 , 91 ].…”

“…After encountering endogenous self-antigens through their TCR in the thymus or extrathymic organs, these natural T-IELs rapidly populate the T-IEL compartment [ 22 , 80 , 87 , 88 , 89 , 90 ]. Despite the fact that the potential extrathymic origin of the TCRαβ + CD8αα + subset remains a topic of debate, it has been generally accepted that they originate in the thymus [ 22 , 42 , 80 , 87 , 91 ]. Both natural T-IEL subsets are considered to be pathogen non-specific due to their selection from self-antigen recognition [ 22 , 92 , 93 , 94 , 95 ].…”