Overcoming memory T-cell responses for induction of delayed tolerance in nonhuman primates

Y. Yamada, S. Boskovic, A. Aoyama, T. Murakami, P. Putheti, R. N. Smith, T. Ochiai, O. Nadazdin, I. Koyama, O. Boenisch, N. Najafian, M. K. Bhasin, R. B. Colvin, J. C. Madsen, T. B. Strom, D. H. Sachs, G. Benichou, A. B. Cosimi, T. Kawai

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65 Citations (Scopus)

Abstract

The presence of alloreactive memory T cells is a major barrier for induction of tolerance in primates. In theory, delaying conditioning for tolerance induction until after organ transplantation could further decrease the efficacy of the regimen, since preexisting alloreactive memory T cells might be stimulated by the transplanted organ. Here, we show that such "delayed tolerance" can be induced in nonhuman primates through the mixed chimerism approach, if specific modifications to overcome/avoid donor-specific memory T-cell responses are provided. These modifications include adequate depletion of CD8+ memory T cells and timing of donor bone marrow administration to minimize levels of proinflammatory cytokines. Using this modified approach, mixed chimerism was induced successfully in 11 of 13 recipients of previously placed renal allografts and long-term survival without immunosuppression could be achieved in at least 6 of these 11 animals.

Original languageEnglish
Pages (from-to)330-340
Number of pages11
JournalAmerican Journal of Transplantation
Volume12
Issue number2
DOIs
Publication statusPublished - 2012 Feb 1
Externally publishedYes

Keywords

  • Donor bone marrow transplantation
  • kidney transplantation
  • memory T cells
  • mixed chimerism
  • nonhuman primates
  • tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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  • Cite this

    Yamada, Y., Boskovic, S., Aoyama, A., Murakami, T., Putheti, P., Smith, R. N., Ochiai, T., Nadazdin, O., Koyama, I., Boenisch, O., Najafian, N., Bhasin, M. K., Colvin, R. B., Madsen, J. C., Strom, T. B., Sachs, D. H., Benichou, G., Cosimi, A. B., & Kawai, T. (2012). Overcoming memory T-cell responses for induction of delayed tolerance in nonhuman primates. American Journal of Transplantation, 12(2), 330-340. https://doi.org/10.1111/j.1600-6143.2011.03795.x