Intestinal Intraepithelial Lymphocytes Include Precursors Committed to the T Cell Receptor α β Lineage

• Published in: Proceedings of the National Academy of Sciences - PNAS 1998-08, Vol.95 (16), p.9459-9464
• Main Authors: Page, Stephanie T., Bogatzki, Lisa Y., Hamerman, Jessica A., Sweenie, Claire H., Hogarth, Philip J., Malissen, Marie, Perlmutter, Roger M., Pullen, Ann M.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - immunology; B lymphocytes; Base Sequence; Cell Lineage; Developmental biology; DNA Primers; Gene rearrangement; Immunophenotyping; Intestines - cytology; Intestines - immunology; Lymphocytes - cytology; Lymphocytes - immunology; Mice; Mice, Inbred C57BL; Polymerase chain reaction; Receptors, Antigen, T-Cell, alpha-beta - immunology; Receptors, Antigen, T-Cell, gamma-delta - immunology; T cell antigen receptors; T cell receptor genes; T lymphocytes; T lymphoid precursor cells; Thymocytes
• ISSN: 0027-8424
• DOI: 10.1073/pnas.95.16.9459

The majority of T cells develop in the thymus and exhibit well characterized phenotypic changes associated with their maturation. Previous analysis of intestinal intraepithelial lymphocytes (IEL) from nude mice and a variety of experimentally manipulated models led to the view that at least a portion of these cells represent a distinct T cell population that matures extrathymically. The IEL that are postulated to mature within the intestine include both T cell receptor (TCR) α β - and γ δ -bearing subpopulations. They can be distinguished from conventional thymically derived T cells in that they express an unusual coreceptor, a CD8α homodimer. In addition, they can utilize the Fc receptor γ -chain in place of the CD3-associated ζ -chain for TCR signaling and their maturation depends on the interleukin 2 receptor β -chain. Moreover, TCRα β+CD8α α+IEL are not subject to conventional thymic selection processes. To determine whether CD3-CD8α α+IEL represent precursors of T cells developing extrathymically, we examined IEL from knockout mice lacking the recombination activating gene-1 (rag-1), CD3ε , or both Lck and Fyn, in which thymic T cell development is arrested. CD3-CD8α α+CD16+IEL from all three mutant strains, as well as from nude mice, included cells that express pre-TCRα transcripts, a marker of T cell commitment. These IEL from lck-/-fyn-/-animals exhibited TCR β -gene rearrangement. However, CD3-CD8α α+CD16+IEL from ε -deficient mice had not undergone Dβ -Jβ joining, despite normal rearrangement at the TCRβ locus in thymocytes from these animals. These results revealed another distinction between thymocytes and IEL, and suggested an unexpectedly early role for CD3ε in IEL maturation.