THYMUS ONTOGENY AND THE DEVELOPMENT OF TCR ALPHA-BETA INTESTINAL INTRAEPITHELIAL LYMPHOCYTES

Murine T cell receptor (TCR) alpha beta intestinal intraepithelial lym phocytes (IEL), which express the CD8 molecule as a homodimer (CD8 alp ha alpha), can be divided into two subsets: those which are CD4(+) (CD 4(+)CD8(+) alpha alpha) and those which are CD4(-) (CD4(-)CD8(+) alpha alpha). Here, we demonstrate that most TCR alpha beta CD4(+)CD8(+) al pha 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 o n Day 3 nearly eliminated both subsets. To further support this hypoth esis, 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 subse ts is generated depends largely on the age of the thymus. The thymus f rom fetal up to 2 weeks of age generates predominantly TCR alpha beta CD4(-)CD8(+) alpha alpha IEL, but very scant amounts CD4(+)CD8(+) alph a alpha IEL. In contrast, the thymus after 2 weeks of age generates ve ry little TCR alpha beta CD4(-)CD8(+) alpha alpha IEL, but generates a n abundant amount of TCR alpha beta CD4(+)CD8(+) alpha alpha IEL. Thes e results are consistent with the observation in euthymic mice that TC R alpha beta CD4(-)CD8(+) alpha alpha IEL precede the appearance of TC R alpha beta CD4(+)CD8(+) alpha alpha IEL by several weeks, thus furth er suggesting that the thymus is the major source of both TCR alpha be ta IEL subsets. (C) 1996 Academic Press, Inc.