T. Lin et al., CD3(-)CD8(+) INTESTINAL INTRAEPITHELIAL LYMPHOCYTES (IEL) AND THE EXTRATHYMIC DEVELOPMENT OF IEL, European Journal of Immunology, 24(5), 1994, pp. 1080-1087
Present evidence suggests that a majority of murine CD3(+) intraepithe
lial intestial lymphocytes (IEL) are etrathymically derived T cells an
d that these extrathymically derived IEL phenotypically expressed the
CD8 homodimer (CD8 alpha alpha). Recently, CD3(-) IEL have been report
ed to express the recombination activating gene (RAG-1), suggesting th
at precursors to extrathymically derived CD3(+)CD8(+)alpha alpha IEL e
xist on the intestinal epithelium. To study in detail whether these CD
3(-) IEL can develop into CD3(+)CD8(+)alpha alpha IEL, we analyzed the
CD3(-)CD8(-) and CD3(-)CD8(+) IEL. We show that (1) CD3(-)CD8(-) IEL
are mostly small, nongranular and phenotypically Pgp-1(+) IL-2R(+) B22
0(-), while CD3(-)CD8(+) IEL are mostly large, granular and phenotypic
ally Pgp-1(-)IL-2R(+) B220(+), (2) CD3(-)CD8(+) IEL express the RAG-1
gene, and (3) CD3(-)CD8(-), CD3(-)CD8(+) and CD3(+)CD8(+)alpha alpha I
EL, respectively, appear sequentially in normal ontogeny and in bone m
arrow-reconstituted thymectomized radiation chimeras. In the latter, v
irtually all CD3(+)CD8(+)alpha alpha IEL expressed the gamma delta T c
ell receptor (TCR), but not the alpha beta TCR. From this and what is
presently known about T cell development, we propose that CD3(-)CD8(+)
IEL are an intermediate in extrathymic IEL development and that the d
evelopment of extrathymically derived IEL occurs at the intestinal epi
thelium from CD3(-)CD8(-) to CD3(-)CD8(+) to CD3(+)(gamma delta TCR)CD
8+alpha alpha.