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B lymphocyte–directed immunotherapy promotes long-term islet allograft survival in nonhuman primates

Nature Medicine volume 13, pages 1295–1298 (2007)Cite this article

Abstract

We found that an induction immunotherapy regimen consisting of rabbit anti-thymocyte globulin (Thymoglobulin) and the monoclonal antibody to CD20 rituximab (Rituxan) promoted long-term islet allograft survival in cynomolgus macaques maintained on rapamycin monotherapy. B lymphocyte reconstitution after rituximab-mediated depletion was characterized by a preponderance of immature and transitional cells, whose persistence was associated with long-term islet allograft survival. Development of donor-specific alloantibodies was abrogated only in the setting of continued rapamycin monotherapy.

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Figure 1: Metabolic, histological and immunological characterization of representative cynomolgus monkey islet allograft recipients.

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References

  1. Shapiro, A.M. et al. N. Engl. J. Med. 355, 1318–1330 (2006).

    Article  CAS  Google Scholar 

  2. Ryan, E.A. et al. Diabetes 54, 2060–2069 (2005).

    Article  CAS  Google Scholar 

  3. Colvin, R.B. & Smith, R.N. Nat. Rev. Immunol. 5, 807–817 (2005).

    Article  CAS  Google Scholar 

  4. Crawford, A., Macleod, M., Schumacher, T., Corlett, L. & Gray, D. J. Immunol. 176, 3498–3506 (2006).

    Article  CAS  Google Scholar 

  5. Noorchashm, H. et al. J. Immunol. 177, 7715–7722 (2006).

    Article  CAS  Google Scholar 

  6. Miller, J.P., Stadanlick, J.E. & Cancro, M.P. J. Immunol. 176, 6405–6410 (2006).

    Article  CAS  Google Scholar 

  7. Préville, X. et al. Transplantation 71, 460–468 (2001).

    Article  Google Scholar 

  8. Martin, F. & Chan, A.C. Annu. Rev. Immunol. 24, 467–496 (2006).

    Article  CAS  Google Scholar 

  9. Edwards, J.C.W. & Cambridge, G. Nat. Rev. Immunol. 6, 394–403 (2006).

    Article  CAS  Google Scholar 

  10. McCulloch, D.K., Koerker, D.J., Kahn, S.E., Bonner-Weir, S. & Palmer, J.P. Diabetes 40, 673–679 (1991).

    Article  CAS  Google Scholar 

  11. Schroder, C. et al. Transpl. Immunol. 12, 19–28 (2003).

    Article  CAS  Google Scholar 

  12. Sims, G.P. et al. Blood 105, 4390–4398 (2005).

    Article  CAS  Google Scholar 

  13. Pascual, V. et al. J. Exp. Med. 180, 329–339 (1994).

    Article  CAS  Google Scholar 

  14. Vugmeyster, Y. et al. Cytometry A 61, 69–75 (2004).

    Article  CAS  Google Scholar 

  15. Cambridge, G. et al. Arthritis Rheum. 54, 723–732 (2006).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Juvenile Diabetes Research Foundation (4-2005-351) and the US National Institutes of Health (AI065356 to A.N. and DK64603 to H.N.). The authors wish to thank M.P. Cancro, A. Jeganathan, M.A. Leonard, R. Mozaffari, N. Noorchashm, L. Rolf and B. Wolf for their helpful input.

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Author notes

  1. Chengyang Liu and Hooman Noorchashm: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA

    Chengyang Liu, Hooman Noorchashm, Taryn Green, Brigitte Koeberlein, Zhonglin Wang, Ergun Velidedeoglu, Susan Y Rostami, Ming Yu, Clyde F Barker & Ali Naji

  2. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA

    Jennifer A Sutter, Mina Naji, Eline Luning Prak, Jean Boyer & John E Tomaszewski

  3. Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA

    Michael R Rickels

  4. Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, 19104, Pennsylvania, USA

    Michelle E Paessler

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  1. Chengyang Liu
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Contributions

C.L. conducted the islet isolations, transplantation, drug administration and immune monitoring of the nonhuman primates with the assistance of Z.W., E.V., M.Y. and T.G. A.N. designed and supervised the experiments. J.A.S. and E.L.P. performed flow cytometric analysis. M.N. and J.B. performed in vitro T and B cell assays. S.Y.R. performed the in vitro mixed lymphocyte reaction assay. M.R.R. performed the in vivo metabolic β cell assays. J.E.T. performed the C4d immunohistochemical analysis. B.K. performed histochemical analysis of tissue biopsies. M.E.P. performed the anti-tetanus responses. Data analysis and manuscript preparation were carried out by C.L., H.N. and A.N. C.F.B. assisted with crucial editing of the manuscript.

Corresponding author

Correspondence to Ali Naji.

Supplementary information

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Supplementary Methods and Supplementary Figs. 1–8 (PDF 8120 kb)

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Liu, C., Noorchashm, H., Sutter, J. et al. B lymphocyte–directed immunotherapy promotes long-term islet allograft survival in nonhuman primates. Nat Med 13, 1295–1298 (2007). https://doi.org/10.1038/nm1673

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