Acute graft-versus-host disease without costimulation via CD28.
T lymphocyte activity is enhanced by costimulatory signals mediated through CD28 binding to B7-1/B7-2 on antigen-presenting cells. Several recent studies have shown that graft-versus-host disease (GVHD) can be inhibited by in vivo treatment with CTLA4Ig, which blocks CD28-B7 interactions. These findings prompted us to investigate the role of CD28 in acute GVHD, using gene-targeted mice. We performed the experiments in the context of strong allogeneic MHC stimulation (H2(b) anti-H2(d)) and weak stimulation (H2(d) anti-H2(b)). In both directions, efficient in vitro T-cell cytotoxicity and acute lethal GVHD were induced by CD28-deficient lymphocytes, which was only partially delayed when compared with wild-type mice. We conclude that lethal GVHD can develop without costimulation via CD28.
Speiser
D E
DE
Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Bachmann
M F
MF
Shahinian
A
A
Mak
T W
TW
Ohashi
P S
PS
D000069594:Abatacept; D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000627:therapeutic use; D018106:CD28 Antigens / Q000276:immunology*; D060908:CTLA-4 Antigen; D003433:Crosses, Genetic; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control; D018796:Immunoconjugates; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D000069594:Abatacept