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Cells1
*
Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030; and
DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, CA 94304
IL-7-deficient (IL-7-/-) mice have reduced
numbers of B and TCR
ß cells, but lack mature TCR
cells.
Although most T cell development occurs in the thymus, some intestinal
intraepithelial lymphocytes (IEL), including TCR cells, can
develop extrathymically. Epithelial cells in both thymus and intestine
synthesize IL-7, suggesting that TCR cell development could occur
in either site. To evaluate the role of thymic IL-7 in development of
TCR cells, newborn TCRß-deficient (TCRß-/-)
thymi were grafted to IL-7-/- mice. Donor- and
host-derived TCR cells were recovered from thymus grafts, spleen,
and IEL. However, when IL-7-/- thymi were grafted to
TCRß-/- mice, no development of graft-derived TCR
cells occurred, indicating that extrathymic IL-7 did not support
TCR IEL generation from newborn thymic precursors. In contrast,
TCR IEL development occurred efficiently in adult, thymectomized,
irradiated C57BL/6J mice reconstituted with IL-7-/- bone
marrow. This demonstrated that extrathymic development of TCR IEL
required extrathymic IL-7 production. Thus, intrathymic IL-7 was
required for development of thymic TCR cells, while peripheral
IL-7 was sufficient for development of extrathymic TCR IEL.
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