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Short-term homing assay reveals a critical role for lymphocyte function-associated antigen-1 in the hepatic recruitment of lymphocytes in graft-versus-host disease

Sato, T ; Habtezion, A ; Beilhack, A ; Schulz, S ; Butcher, E and Thorlacius, Henrik LU (2006) In Journal of Hepatology 44(6). p.1132-1140
Abstract
Background/Aims: The liver is a major target organ of graft versus host disease (GvHD) with massive infiltration of alloreactive lymphocytes resulting in hepatitis and hepatocyte injury. Although adhesive mechanisms have been implicated in the biology of GvHD hepatitis, the identity of homing receptors involved in the initial recruitment of cells from the blood is not known. Methods: We have developed a short-term homing assay in a model of murine GvHD. Splenocytes from donors at an active stage of GvHD were injected intravenously into adoptive recipients also undergoing GvHD. The recruitment of cells to the liver was assessed 6 h after cell transfer. Results: Activated donor CD8 and CD4 lymphocytes expressed lymphocyte function antigen-1... (More)
Background/Aims: The liver is a major target organ of graft versus host disease (GvHD) with massive infiltration of alloreactive lymphocytes resulting in hepatitis and hepatocyte injury. Although adhesive mechanisms have been implicated in the biology of GvHD hepatitis, the identity of homing receptors involved in the initial recruitment of cells from the blood is not known. Methods: We have developed a short-term homing assay in a model of murine GvHD. Splenocytes from donors at an active stage of GvHD were injected intravenously into adoptive recipients also undergoing GvHD. The recruitment of cells to the liver was assessed 6 h after cell transfer. Results: Activated donor CD8 and CD4 lymphocytes expressed lymphocyte function antigen-1 (LITA-1), alpha 4-integrins, and P-selectin binding ligands, and localized more efficiently than naive T cells. Immunoneutralization of LFA-1 reduced the recruitment of CD8 and CD4 lymphocytes to the liver by more than 60%. Anti-LFA-1 antibody also markedly reduced infiltration of lymphocytes in periportal areas and protected against hepatocellular damage. Conclusions: We demonstrate a critical role of LFA-1 in the recruitment of activated lymphocytes to the liver and in immune-cell mediated hepatitis. LFA-1 may be an effective therapeutic target for protecting the liver following bone marrow transplantation. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
liver, integrins, adhesion molecules, cell trafficking, selectins
in
Journal of Hepatology
volume
44
issue
6
pages
1132 - 1140
publisher
Elsevier
external identifiers
  • wos:000237984400016
  • pmid:16466827
  • scopus:33646161208
  • pmid:16466827
ISSN
0168-8278
DOI
10.1016/j.jhep.2005.11.042
language
English
LU publication?
yes
id
b508acf9-d252-4553-91c3-eaf047dd2a22 (old id 407422)
date added to LUP
2016-04-01 11:47:11
date last changed
2020-04-01 02:58:13
@article{b508acf9-d252-4553-91c3-eaf047dd2a22,
  abstract     = {Background/Aims: The liver is a major target organ of graft versus host disease (GvHD) with massive infiltration of alloreactive lymphocytes resulting in hepatitis and hepatocyte injury. Although adhesive mechanisms have been implicated in the biology of GvHD hepatitis, the identity of homing receptors involved in the initial recruitment of cells from the blood is not known. Methods: We have developed a short-term homing assay in a model of murine GvHD. Splenocytes from donors at an active stage of GvHD were injected intravenously into adoptive recipients also undergoing GvHD. The recruitment of cells to the liver was assessed 6 h after cell transfer. Results: Activated donor CD8 and CD4 lymphocytes expressed lymphocyte function antigen-1 (LITA-1), alpha 4-integrins, and P-selectin binding ligands, and localized more efficiently than naive T cells. Immunoneutralization of LFA-1 reduced the recruitment of CD8 and CD4 lymphocytes to the liver by more than 60%. Anti-LFA-1 antibody also markedly reduced infiltration of lymphocytes in periportal areas and protected against hepatocellular damage. Conclusions: We demonstrate a critical role of LFA-1 in the recruitment of activated lymphocytes to the liver and in immune-cell mediated hepatitis. LFA-1 may be an effective therapeutic target for protecting the liver following bone marrow transplantation. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.},
  author       = {Sato, T and Habtezion, A and Beilhack, A and Schulz, S and Butcher, E and Thorlacius, Henrik},
  issn         = {0168-8278},
  language     = {eng},
  number       = {6},
  pages        = {1132--1140},
  publisher    = {Elsevier},
  series       = {Journal of Hepatology},
  title        = {Short-term homing assay reveals a critical role for lymphocyte function-associated antigen-1 in the hepatic recruitment of lymphocytes in graft-versus-host disease},
  url          = {http://dx.doi.org/10.1016/j.jhep.2005.11.042},
  doi          = {10.1016/j.jhep.2005.11.042},
  volume       = {44},
  year         = {2006},
}