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Costimulatory blockade by the induction of an endogenous xenospecific antibody response

Nature Immunology volume 1, pages 163–168 (2000)Cite this article

Abstract

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.

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Figure 1: Sequence and structure of chimeric peptide 6.
Figure 2: Induction of antibodies to peptide.
Figure 3: Species-specific recognition of native pCD86 by OVA-pCD86 peptide antisera.
Figure 4: Specific recognition of OVA(323–339) epitope by T cells from OVA-pCD86 peptide–sensitized mice.
Figure 5: Effect of anti-peptide on the delivery of costimulation by pCD86 and mCD86 as determined by T cell proliferation.
Figure 6: OVA-pCD86 peptide immunization prolongs the survival of transplanted porcine pancreatic islets.

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Acknowledgements

We thank G. Taylor for assistance in the selection and design of the chimeric peptides, A.Chaudry for help with statistical analysis, H. Reiser for the donation of CHO transfectants, and H. Stauss and A. George for reading the manuscript. Supported by ML laboratories, St. Albans, Hertfordshire; additional funding was provided by PPL Laboratories, Scotland.

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  1. Department of Immunology, Imperial College of Science Technology and Medicine, Hammersmith Campus, Du Cane Road, London, W12 ONN, UK

    Nicola J. Rogers, Vincenzo Mirenda, Ian Jackson, Anthony Dorling & Robert I. Lechler

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  1. Nicola J. Rogers
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Correspondence to Robert I. Lechler.

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Rogers, N., Mirenda, V., Jackson, I. et al. Costimulatory blockade by the induction of an endogenous xenospecific antibody response. Nat Immunol 1, 163–168 (2000). https://doi.org/10.1038/77853

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