Thymus ontogeny and the development of TCR alpha beta intestinal intraepithelial lymphocytes.
Murine T cell receptor (TCR) alpha beta intestinal intraepithelial lymphocytes (IEL), which express the CD8 molecule as a homodimer (CD8 alpha alpha), can be divided into two subsets: those which are CD4+ (CD4+CD8+alpha alpha) and those which are CD4- (CD4-CD8+alpha alpha). Here, we demonstrate that most TCR alpha beta CD4+CD8+alpha alpha IEL and TCR alpha beta CD4-CD8+alpha alpha IEL subsets appear to be of thymus origin, as neonatal thymectomy of BALB/c mice on Day 3 nearly eliminated both subsets. To further support this hypothesis, we demonstrate by grafting the thymus of CBF1 (BALB/c x C57BL/6) mice into nude mice that the thymus is capable of generating both TCR alpha beta CD4-CD8+alpha alpha IEL and TCR alpha beta CD4+CD8+alpha alpha IEL. However, which of the two TCR alpha beta IEL subsets is generated depends largely on the age of the thymus. The thymus from fetal up to 2 weeks of age generates predominantly TCR alpha beta CD4-CD8+alpha alpha IEL, but very scant amounts CD4+CD8+alpha alpha IEL. In contrast, the thymus after 2 weeks of age generates very little TCR alpha beta CD4-CD8+alpha alpha IEL, but generates an abundant amount of TCR alpha beta CD4+CD8+alpha alpha IEL. These results are consistent with the observation in euthymic mice that TCR alpha beta CD4-CD8+alpha alpha IEL precede the appearance of TCR alpha beta CD4+CD8+alpha alpha IEL by several weeks, thus further suggesting that the thymus is the major source of both TCR alpha beta IEL subsets.
Lin
T
T
Section of Gastroentrology, University of Wisconsin Hospitals, Middleton 53792, USA.
Matsuzaki
G
G
Yoshida
H
H
Kenai
H
H
Omoto
K
K
Umesue
M
M
Singaram
C
C
Nomoto
K
K
D000375:Aging / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D005314:Embryonic and Fetal Development / Q000276:immunology; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D018448:Models, Immunological; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000166:cytology*; D013950:Thymus Gland / Q000254:growth & development* / Q000276:immunology* / Q000637:transplantation
D016693:Receptors, Antigen, T-Cell, alpha-beta