LPAM(47 integrin) is an important homing integrin on alloreactive T cells in the development of intestinal graft-versus-host disease
From the Department of Pediatrics and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville; Department of Pathology, Thomas Jefferson Medical Center, Philadelphia, PA; and Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY.-9[|3g{, 百拇医药
Lymphocyte Peyer patch adhesion molecule (LPAM) or {alpha} 4{beta} 7 integrin is expressed on lymphocytes and is responsible for T-cell homing into gut-associated lymphoid tissues through its binding to mucosal addressin cell adhesion molecule (MAdCAM), which is present on high endothelial venules of mucosal lymphoid organs. We found in murine allogeneic bone marrow transplantation (BMT) models that recipients of {alpha} 4{beta} 7– donor T cells had significantly less graft-versus-host disease (GVHD) morbidity and mortality compared with recipients of {alpha} 4{beta} 7+ donor T cells. A kinetic posttransplantation analysis of lymphocytes in the intestines and mesenteric lymph nodes demonstrated a delayed invasion of lower numbers of {alpha} 4{beta} 7+ T cells in recipients of {alpha} 4{beta} 7– T cells compared with recipients of {alpha} 4{beta} 7+ T cells. Histopathologic analysis of GVHD target organs revealed that recipients of {alpha} 4{beta} 7– T cells developed less GVHD of the intestines and liver, whereas there was no difference in cutaneous and thymic GVHD between recipients of {alpha} 4{beta} 7– or {alpha} 4{beta} 7+ T cells. Finally, we found that in vivo GVT activity of {alpha} 4{beta} 7– donor T cells was preserved. We conclude that the {alpha} 4{beta} 7 integrin is important for the invasion of alloreactive donor T cells into the gut and the subsequent development of intestinal GVHD and overall GVHD morbidity and mortality.(Aleksandra Petrovic Onder Alpdogan Lucy M. Willis Jeffrey M. Eng Andrew S. Greenberg Barry J. Kappel)
Lymphocyte Peyer patch adhesion molecule (LPAM) or {alpha} 4{beta} 7 integrin is expressed on lymphocytes and is responsible for T-cell homing into gut-associated lymphoid tissues through its binding to mucosal addressin cell adhesion molecule (MAdCAM), which is present on high endothelial venules of mucosal lymphoid organs. We found in murine allogeneic bone marrow transplantation (BMT) models that recipients of {alpha} 4{beta} 7– donor T cells had significantly less graft-versus-host disease (GVHD) morbidity and mortality compared with recipients of {alpha} 4{beta} 7+ donor T cells. A kinetic posttransplantation analysis of lymphocytes in the intestines and mesenteric lymph nodes demonstrated a delayed invasion of lower numbers of {alpha} 4{beta} 7+ T cells in recipients of {alpha} 4{beta} 7– T cells compared with recipients of {alpha} 4{beta} 7+ T cells. Histopathologic analysis of GVHD target organs revealed that recipients of {alpha} 4{beta} 7– T cells developed less GVHD of the intestines and liver, whereas there was no difference in cutaneous and thymic GVHD between recipients of {alpha} 4{beta} 7– or {alpha} 4{beta} 7+ T cells. Finally, we found that in vivo GVT activity of {alpha} 4{beta} 7– donor T cells was preserved. We conclude that the {alpha} 4{beta} 7 integrin is important for the invasion of alloreactive donor T cells into the gut and the subsequent development of intestinal GVHD and overall GVHD morbidity and mortality.(Aleksandra Petrovic Onder Alpdogan Lucy M. Willis Jeffrey M. Eng Andrew S. Greenberg Barry J. Kappel)