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

研究成果: Article査読

74 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)330-340
ページ数11
ジャーナルAmerican Journal of Transplantation
12
2
DOI
出版ステータスPublished - 2012 2
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 移植
  • 薬理学(医学)

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