Thymus Ontogeny and the Development of TCR αβ Intestinal Intraepithelial Lymphocytes

Murine T cell receptor (TCR) αβ intestinal intraepithelial lymphocytes (IEL), which express the CD8 molecule as a homodimer (CD8αα), can be divided into two subsets: those which are CD4+(CD4+CD8+αα) and those which are CD4−(CD4−CD8+αα). Here, we demonstrate that most TCR αβ CD4+CD8+αα IEL and TCR αβ CD4−CD8+αα 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 × C57BL/6) mice into nude mice that the thymus is capable of generating both TCR αβ CD4−CD8+αα IEL and TCR αβ CD4+CD8+αα IEL. However, which of the two TCR αβ 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 αβ CD4−CD8+αα IEL, but very scant amounts CD4+CD8+αα IEL. In contrast, the thymus after 2 weeks of age generates very little TCR αβ CD4−CD8+αα IEL, but generates an abundant amount of TCR αβ CD4+CD8+αα IEL. These results are consistent with the observation in euthymic mice that TCR αβ CD4−CD8+αα IEL precede the appearance of TCR αβ CD4+CD8+αα IEL by several weeks, thus further suggesting that the thymus is the major source of both TCR αβ IEL subsets.