CD3CD8+ intestinal intraepithelial lymphocytes (IEL) and the extrathymic development of IEL

T Lin, G Matsuzaki, H Yoshida… - European journal of …, 1994 - Wiley Online Library
T Lin, G Matsuzaki, H Yoshida, N Kobayashi, H Kenai, K Omoto, K Nomoto
European journal of immunology, 1994Wiley Online Library
Present evidence suggests that a majority of murine CD3+ intraepithelial intestinal
lymphocytes (IEL) are extrathymically derived T cells and that these extrathymically derived
IEL phenotypically express the CD8 homodimer (CD8αα). Recently, CD3− IEL have been
reported to express the recombination activating gene (RAG‐1), suggesting that precursors
to extrathymically derived CD3+ CD8+ αα IEL exist on the intestinal epithelium. To study in
detail whether these CD3− IEL can develop into CD3+ CD8+ αα IEL, we analyzed the CD3 …
Abstract
Present evidence suggests that a majority of murine CD3+ intraepithelial intestinal lymphocytes (IEL) are extrathymically derived T cells and that these extrathymically derived IEL phenotypically express the CD8 homodimer (CD8αα). Recently, CD3 IEL have been reported to express the recombination activating gene (RAG‐1), suggesting that precursors to extrathymically derived CD3+CD8+αα IEL exist on the intestinal epithelium. To study in detail whether these CD3 IEL can develop into CD3+CD8+αα IEL, we analyzed the CD3 IEL subset and found that it can be separated into two subsets, namely CD3CD8 and CD3CD8+ IEL. We show that (1) CD3CD8 IEL are mostly small, non‐granular and phenotypically Pgp‐1+ IL‐2R+ B220, while CD3CD8+ IEL are mostly large, granular and phenotypically Pgp‐1 IL‐2R+ B220+, (2) CD3‐CD8+ IEL express the RAG‐1 gene, and (3) CD3CD8, CD3CD8+ and CD3+CD8+αα IEL, respectively, appear sequentially in normal ontogeny and in bone marrow‐reconstituted thymectomized radiation chimeras. In the latter, virtually all CD3+CD8+αα IEL expressed the γδ T cell receptor (TCR), but not the αβ TCR. From this and what is presently known about T cell development, we propose that CD3CD8+ IEL are an intermediate in extrathymic IEL development and that the development of extrathymically derived IEL occurs at the intestinal epithelium from CD3CD8 to CD3CD8+ to CD3+(γδ TCR)CD8+αα.
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