Year: 2008
Type: article
Abstract: Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation. Migration of donor-derived T cells into GVHD target organs plays an essential role in the development of GVHD. β2 integrins are critically important for leukocyte extravasation through vascular endothelia and for T cell activation. We asked whether CD18-deficient T cells would induce less GVHD while sparing graft-versus-leukemia (GVL) effect. In murine allogeneic bone marrow transplantation models, we found that recipients of CD18-/- donor T cells had significantly less GVHD morbidity and mortality compared with recipients of WT donor T cells. Analysis of allo-reactivity showed that CD18-/- and WT T cells had comparable activation, expansion and cytokine production in vivo. Reduced GVHD was associated with a significant decrease in donor-T cell infiltration of recipient intestine and with an overall decrease in pathologic scores in intestine and liver. Finally, we found that in vivo GVL effect of CD18-/- donor T cells was largely preserved, because mortality of the recipients transplanted with CD18-/- T cells plus tumor cells was greatly delayed or prevented. Our data suggest that strategies to target β2 intergrin have clinical potential to alleviate or prevent GVHD while sparing GVL activity.
Authors: X.-Z. Yu, Y. Liang, C. Liu, J.Y. Djeu, B. Zhong, T. Peters, K. Scharffetter-Kochanek, C. Anasetti
Institutions: Moffitt Cancer Center, University of Florida, Universität Ulm
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W2155301284