CD8aa+ intraepithelial lymphocytes recruited from peripheral CD4+ and CD8+ T cells represent functionally distinct lineages

The TCRaß CD8aa+ intraepithelial lymphocytes (IELs) play a significant role in primary immune defence in the small intestine. The canonical model of their development distinguishes TCRaß IELs into induced and natural (TCRaß CD8aa+) types, each influenced by distinct developmental pathways and antigen encounters. It is believed that natural CD8aa+ IELs differentiate solely from triple positive (TP) CD4+CD8aß+CD8aa+ thymic progenitors that recognized self MHC-peptide complexes with high affinity but avoided deletion during selection. Our investigation reveals that, in addition to this central commitment, the CD8aa+ IELs undergo in situ enrichment through recruitment from peripheral CD4+ and CD8aß+ T cell populations. We found that the functional makeup of individual clones within the CD8aa+ IEL subset is dictated by their origin. We demonstrate that expression of Bmp7 or Ly49 (Ly49C, F, H, and I) serve as markers indicating the CD8aa+ IELs' peripheral provenance: CD8aß+ and CD4+ T lymphocytes, respectively. Overall design: Rag2–/– animals were intravenously (i.v.) injected with ether conventional CD4+ T cells or CD8aß+ T cell isolated from the LN of Themis WT. Each of the Rag2–/– recipients received minimum 2x106 T cells in single i.v. injection. After one week from adoptive transfer of T cells, the mLN and small intestine tissues were collected for further investigation. The RNA was isolated from sorted TCRß CD8aa+, TCRß CD8aß+ and TCRß CD4+ IEL, expanded/developed in Rag2–/– host.