Prevention of acute graft-versus-host disease by blocking T-cell entry to secondary lymphoid organs.
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.
Beilhack
Andreas
A
Department of Medicine, Stanford University, 269 W. Campus Drive, Stanford, CA 94305, USA.
Schulz
Stephan
S
Baker
Jeanette
J
Beilhack
Georg F
GF
Nishimura
Ryosei
R
Baker
Enosh M
EM
Landan
Gilad
G
Herman
Edward I
EI
Butcher
Eugene C
EC
Contag
Christopher H
CH
Negrin
Robert S
RS
D000818:Animals; D002465:Cell Movement; D045142:Cross-Priming; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D008198:Lymph Nodes / Q000473:pathology; D008221:Lymphoid Tissue / Q000473:pathology*; D051379:Mice; D009928:Organ Specificity; D010581:Peyer's Patches / Q000473:pathology; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*; D019172:Transplantation Conditioning; D051598:Whole Body Imaging
D016201:Receptors, Lymphocyte Homing