MURINE ISOGRAFT STUDIES OF GUT IMMUNITY - RECIRCULATION AND HOMING OFMONONUCLEAR-CELLS

Background & Aims: Recirculation of lymphocytes requires appropriate s ignals on the lymphocytes as well as the vascular endothelium. The aim of this report was to study the expression of the mucosal addressin r equired for Peyer's patch-selective lymphocyte homing during ontogeny of the murine intestine and investigate the role of this addressin in recirculation of mononuclear cells, Methods: Immunohistochemistry and murine intestinal isografts were used in which the small intestine fro m neonatal mice is implanted subcutaneously in mice with severe combin ed immunodeficiency disease, Results: Expression of the mucosal addres sin cell adhesion molecule 1 during murine intestinal ontogeny was det ected from embryonic day 15 in developing gut and in adult Peyer's pat ches and lamina propria, Isografted intestine developed normally; it w as not exposed to luminal contents but expressed the mucosal addressin cell adhesion molecule 1, Mononuclear cells recirculated to native an d isografted intestine and recirculation was inhibited by monoclonal a ntibody to mucosal addressin in a regionally specific manner with grea test inhibition in the distal intestine, Conclusions: The mucosal vasc ular addressin is expressed early in ontogeny and can be detected in l amina propria in addition to Peyer's patches of the gut, The isograft not only developed into a morphologically normal intestine but also ex pressed differentiation antigens required for normal lymphoid homing t o gut without exposure to luminal contents or lymphocytes.