PIG LYMPHOCYTES UTILIZE MOUSE MADCAM-1 TO ENTER FETAL GUT XENOGRAFTS IN SCID MICE

Ileocecal junction (ICJ) and proximal intestine (PI) fragments hom CD4 5(323-) allovariant fetal pigs were grafted subcutaneously into SCID m ice. The xenografts were examined 8-12 weeks later using two-color imm unohistology and the ICJ, but not PI, xenografts were found to contain three types of vessels. The first (the majority) was lined with mouse endothelium (mAb 9F1(+)), the second was lined with pig endothelium, and the third was chimeric. The ICJ vessels were specifically lined wi th mouse endothelium expressing MAdCAM-1, the mucosal addressin. Vesse ls lined with pig endothelium alone did not express the MAdCAM-1 epito pes. Radiolabeled allovariant pig peripheral blood lymphocytes (PBL) w ere introduced i.v. into the xenografted SCID mice, and entry into xen ografts studied. Pig PBL were occasionally seen in MECA-367(+) vessel walls after 4 h and within the ICJ but not PI xenografts after 24 h. T his entry was specifically blocked by coinjection of the anti-MAdCAM-1 mAb MECA-367. The results demonstrate reendothelialization of xenogra fts by host endothelium that expresses its own addressin and is functi onal for xenogenic PBL. (C) 1997 Academic Press.