Lymphocyte Peyer patch adhesion molecule (LPAM) or α 4β7 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 α4β7- donor T cells had significantly less graft-versus-host disease (GVHD) morbidity and mortality compared with recipients of α4β7+ donor T cells. A kinetic posttransplantation analysis of lymphocytes in the intestines and mesenteric lymph nodes demonstrated a delayed invasion of lower numbers of α4β7+ T cells in recipients of α4β7- T cells compared with recipients of α4β7+ T cells. Histopathologic analysis of GVHD target organs revealed that recipients of α4β7- T cells developed less GVHD of the intestines and liver, whereas there was no difference in cutaneous and thymic GVHD between recipients of α4β7 - or α4β7+ T cells. Finally, we found that in vivo GVT activity of α4β 7- donor T cells was preserved. We conclude that the α4β7 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.
All Science Journal Classification (ASJC) codes
- Cell Biology