Identification of Pre- and Postselection TCR[alpha][beta]+ Intraepithelial Lymphocyte Precursors in the Thymus

• Published in: Immunity (Cambridge, Mass.) Vol. 25; no. 4; p. 631
• Main Authors: Gangadharan, Denise, Lambolez, Florence, Attinger, Antoine, Wang-Zhu, Yiran, Sullivan, Barbara A, Cheroutre, Hilde
• Format: Journal Article
• Language: English
• Published: Cambridge Elsevier Limited 01.10.2006
• Subjects: Cell culture; Genotype & phenotype; Lymphocytes; Peptides; Rodents; T cell receptors
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2006.08.018

The immune system preserves and makes use of autoreactive lymphocytes with specialized functions. Here we showed that one of these populations, CD8αα+TCRαβ+intestinal intraepithelial lymphocytes (IELs), arose from a unique subset of double-positive thymocytes. This subset of cells was precommitted to preferentially give rise to CD8αα+TCRαβ+IELs, but they required exposure to self-agonist peptides. The agonist-selected TCRαβ+thymocytes are CD4 and CD8 double-negative, and their final maturation, including the induction of CD8αα expression, appeared to occur only after thymus export in the IL-15-rich environment of the gut. These developmental steps, including precommitment of immature thymocytes, TCR-mediated agonist selection, and postthymic differentiation promoted by cytokines, define a unique pathway for the generation of CD8αα+TCRαβ+IEL.