Costimulation pathways in host immune responses to allogeneic hepatocytes.
BACKGROUND
This study investigated the role of the CD28/B7 (blocked by CTLA4Ig) and CD40/CD40L (blocked by MR1) costimulation pathways on in vivo host T-cell- mediated immune responses to allogeneic hepatocytes.


METHODS
Survival of allogeneic hepatocytes (H-2q) in C57BL/6 (H-2b) mice untreated or treated with MR1, CTLA4Ig, L6 (control fusion protein), or a combination of MR1 and CTLA4Ig fusion protein was determined.


RESULTS
Median survival time for hepatocellular allografts was 10, 84, 10, 10, and 84 days in untreated (n= 10), MR1-treated (n=7) (P<.0001), CTLA4Ig-treated (n=7) (P=0.02), L6-treated (n=3) (P, not significant), and the combination of MR1- and CTLA4Ig-treated (n=6) (P=0.0003) groups, respectively.


CONCLUSIONS
Host treatment with MR1, but not CTLA4Ig, prolonged hepatocellular allograft survival. These data suggest that CD28/B7 interactions appear relatively unimportant, whereas CD40/CD40L interactions provide critical costimulator signals for T-cell-dependent immune responses to allogeneic hepatocytes.
Bumgardner
G L
GL
Department of Surgery, The Ohio State University and Medical Center, Columbus 43210, USA.
Li
J
J
Heininger
M
M
Orosz
C G
CG
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology*; D018106:CD28 Antigens / Q000502:physiology; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D060908:CTLA-4 Antigen; D017690:Cell Transplantation; D006968:Hypersensitivity, Delayed; D018796:Immunoconjugates; D008099:Liver / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D000069594:Abatacept