Intraepithelial Lymphocyte Lineage

CD4 CD8b lymphocytes called unconventional iIELs(Cheroutre et al., 2011). Together with the recently identifiedILC1 subset, these innate-like populations represent long-livedresident lineages that express a conspicuously similar programdominated by the expression of the transcription factor Tbet,expression of natural killer (NK) cell receptors, and interleukin-15 (IL-15)-regulated homeostasis or function (Fuchs et al.,2013). Although there is no complete understanding of the indi-vidual capabilities of each iIEL subset, their similar gene expres-sionprogramssuggestlargelyoverlappingfunctionsthatincludehomeostatic crosstalk with intestinal epithelial cells through theexpression of the herpesvirus entry mediator (HVEM)-receptorCD160, and with microbiota and diet through the expression ofthe aryl hydrocarbon receptor (Ahr) (Li et al., 2011; Shui et al.,2012). They can be rapidly activated in various microbial infec-tions, where they are thought to function independently ofMHC-peptide ligands through various cytolytic stress-specificNK-lineage receptors (Guy-Grand et al., 1996). They can alsopromote repair and regeneration of the epithelium through thesecretion of various growth factors, and they can directly kill in-testinal bacteria through the release of antimicrobial peptides(BoismenuandHavran,1994;Ismailetal.,2011).Althoughthesestriking properties of mucosal host defense have been welldescribed, the origin and development of these innate-like iIELlineages have remained elusive.This is particularly vexing in the case of the TCRab