IL-7 receptor α⁺ CD3^- cells in the embryonic intestine induces the organizing center of Peyer's patches

Peyer's patch (PP) organogenesis proceeds through three histologically distinct steps: formation of organizing centers expressing VCAM-1 and ICAM-1 in segregated regions of the intestine at 15.5 days post-coitus (d.p.c.) (step I), accumulation of blood cells expressing different sets of surface markers to this region at 16.5-17.0 d.p.c. (step II), and entry of CD3⁺ and B220⁺ lymphocytes just before birth (step III). PP formation of both II7ra(-/-) and Lta(-/-) mice is impaired from step I, suggesting involvement of the two molecules at the same timing in PP organogenesis. Expression of lymphotoxin (LT) α and LTβ in IL-7 receptor (IL-7R) α⁺ cells in the intestine indicates that defects of II7ra(-/-) and Lta(-/-) mice are due to functional inability of IL-7Rα⁺ cells in the induction of PP anlage. Blocking of IL-7Rα function by a single injection of the antagonistic mAb in 15.5 d.p.c. embryos suppressed appearance of VCAM-1⁺ spots and expression of LTα and LTβ in the intestine, which eventually resulted in mice without PP but are otherwise normal, Intestinal IL-7Rα⁺ cells are lymphoid in morphology but CD3^- and functional in both nu/nu and Rag2(-/-) mice. These results implicate IL-7Rα⁺ CD3^- cells as the direct inducer of the organizing center of PP.