LPAM (α4β7 integrin) is an important homing integrin on alloreactive T cells in the development of intestinal graft-versus-host disease Journal Article


Authors: Petrovic, A.; Alpdogan, O.; Willis, L. M.; Eng, J. M.; Greenberg, A. S.; Kappel, B. J.; Liu, C.; Murphy, G. J.; Heller, G.; van den Brink, M. R. M.
Article Title: LPAM (α4β7 integrin) is an important homing integrin on alloreactive T cells in the development of intestinal graft-versus-host disease
Abstract: 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. © 2004 by The American Society of Hematology.
Keywords: controlled study; protein expression; leukemia; unclassified drug; histopathology; mortality; nonhuman; protein function; protein localization; t lymphocyte; t-lymphocytes; animal cell; mouse; animals; mice; animal tissue; morbidity; animal experiment; animal model; allogenic bone marrow transplantation; mice, inbred c57bl; skin; liver; donor; cellular immunity; vascular endothelium; thymus; lymphoma; graft versus host reaction; cell count; venule; peyer's patches; mice, inbred cba; bone marrow transplantation; graft vs host disease; isoantigens; intestine; integrin; integrins; alloimmunity; intestinal mucosa; peyer patch; mucosal addressin cell adhesion molecule 1; mesentery lymph node; female; priority journal; article; lymphocyte peyer patch adhesion molecule
Journal Title: Blood
Volume: 103
Issue: 4
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2004-02-15
Start Page: 1542
End Page: 1547
Language: English
DOI: 10.1182/blood-2003-03-0957
PROVIDER: scopus
PUBMED: 14563643
DOI/URL:
Notes: Blood -- Cited By (since 1996):65 -- Export Date: 16 June 2014 -- CODEN: BLOOA -- Source: Scopus
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MSK Authors
  1. Glenn Heller
    303 Heller
  2. Lucy Willis
    27 Willis
  3. Jeffrey Eng
    36 Eng
  4. Barry J Kappel
    28 Kappel