Prevention of acute graft-versus-host disease by blocking T-cell entry to secondary lymphoid organs
- 1 March 2008
- journal article
- Published by American Society of Hematology in Blood
- Vol. 111 (5), 2919-2928
- https://doi.org/10.1182/blood-2007-09-112789
Abstract
In acute graft-versus-host disease (aGVHD), donor T cells attack the recipient's gastrointestinal tract, liver, and skin. We hypothesized that blocking access to distinct lymphoid priming sites may alter the specific organ tropism and prevent aGVHD development. In support of this initial hypothesis, we found that different secondary lymphoid organs (SLOs) imprint distinct homing receptor phenotypes on evolving alloreactive effector T cells in vivo. Yet preventing T-cell entry to specific SLOs through blocking monoclonal antibodies, or SLO ablation, did not alter aGVHD pathophysiology. Moreover, transfer of alloreactive effector T cells into conditioned secondary recipients targeted the intestines and liver, irrespective of their initial priming site. Thus, we demonstrate redundancy of SLOs at different anatomical sites in aGVHD initiation. Only prevention of T-cell entry to all SLOs could completely abrogate the onset of aGVHD.Keywords
This publication has 51 references indexed in Scilit:
- An inflammatory checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral tissuesThe Journal of Experimental Medicine, 2006
- Gut-associated lymphoid tissue–primed CD4+ T cells display CCR9-dependent and -independent homing to the small intestineBlood, 2006
- In vivo analyses of early events in acute graft-versus-host disease reveal sequential infiltration of T-cell subsetsBlood, 2005
- Sequential Expression of Adhesion and Costimulatory Molecules in Graft-versus-Host Disease Target Organs after Murine Bone Marrow Transplantation across Minor Histocompatibility Antigen BarriersTransplantation and Cellular Therapy, 2005
- In vivo imaging of graft-versus-host-disease in miceBlood, 2004
- T-cell priming by dendritic cells in lymph nodes occurs in three distinct phasesNature, 2004
- Selective imprinting of gut-homing T cells by Peyer's patch dendritic cellsNature, 2003
- Two-Photon Imaging of Lymphocyte Motility and Antigen Response in Intact Lymph NodeScience, 2002
- Intestinal dendritic cells increase T cell expression of α4β7 integrinEuropean Journal of Immunology, 2002
- Prevention of Graft Versus Host Disease by Inactivation of Host Antigen-Presenting CellsScience, 1999