Costimulatory blockade by the induction of an endogenous xenospecific antibody response.
Xenogeneic tissues induce vigorous T cell immunity, reflecting the ability of costimulatory molecules to function across species barriers. We describe a strategy to inhibit costimulation that exploits species differences using the model of porcine pancreatic islet transplantation into mice. Mice were immunized with chimeric peptides that contained a known T cell epitope and selected sequences of the porcine costimulatory molecule CD86. This resulted in anti-peptide antibody responses that recognized intact porcine CD86, blocked costimulation by porcine CD86 but not murine CD86 in vitro, and prolonged the survival of porcine islet grafts in vivo. This strategy of inducing endogenous donor-specific costimulatory blockade has potential clinical applicability.
Department of Immunology, Imperial College of Science, Technology and Medicine, Hammersmith Campus, Du Cane Road, London W12 ONN, UK.
N J
NJ
Rogers
V
V
Mirenda
I
I
Jackson
A
A
Dorling
R I
RI
Lechler
D000595:Amino Acid Sequence; D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology*; D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology*; D015478:Antigens, Heterophile / Q000276:immunology*; D051940:B7-2 Antigen; D006085:Graft Survival / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D016035:Pancreas Transplantation / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000276:immunology; D013045:Species Specificity; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D000910:Antibodies, Heterophile; D015703:Antigens, CD; D015478:Antigens, Heterophile; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; C111390:OVA 323-339; D010446:Peptide Fragments; D010455:Peptides; D010047:Ovalbumin