CD3-CD8+ intestinal intraepithelial lymphocytes (IEL) and the extrathymic development of IEL.
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 (CD8 alpha alpha). Recently, CD3- IEL have been reported to express the recombination activating gene (RAG-1), suggesting that precursors to extrathymically derived CD3+CD8+ alpha alpha IEL exist on the intestinal epithelium. To study in detail whether these CD3-IEL can develop into CD3+CD8+ alpha alpha IEL, we analyzed the CD3-IEL subset and found that it can be separated into two subsets, namely CD3-CD8- and CD3-CD8+ IEL. We show that (1) CD3-CD8- IEL are mostly small, non-granular and phenotypically Pgp-1+ IL-2R+ B220-, while CD3-CD8+ IEL are mostly large, granular and phenotypically Pgp-1- IL-2R+ B220+, (2) CD(3-)-CD8+ IEL express the RAG-1 gene, and (3) CD3-CD8-, CD3-CD8+ and CD3+CD8+ alpha alpha IEL, respectively, appear sequentially in normal ontogeny and in bone marrow-reconstituted thymectomized radiation chimeras. In the latter, virtually all CD3+CD8+ alpha alpha IEL expressed the gamma delta T cell 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 development of extrathymically derived IEL occurs at the intestinal epithelium from CD3-CD8- to CD3-CD8+ to CD3+(gamma delta TCR)CD8+ alpha alpha.
Lin
T
T
Department of Immunology, Kyushu University, Fukuoka, Japan.
Matsuzaki
G
G
Yoshida
H
H
Kobayashi
N
N
Kenai
H
H
Omoto
K
K
Nomoto
K
K
D000818:Animals; D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000502:physiology; D017252:CD3 Complex / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis*; D002454:Cell Differentiation / Q000502:physiology; D005434:Flow Cytometry; D016654:Genes, RAG-1 / Q000502:physiology; D007413:Intestinal Mucosa / Q000254:growth & development / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011828:Radiation Chimera; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D017252:CD3 Complex; D016827:CD8 Antigens