Repeated injections of IL-2 break renal allograft tolerance induced via mixed hematopoietic chimerism in monkeys

Y. Yamada, O. Nadazdin, S. Boskovic, S. Lee, E. Zorn, R. N. Smith, R. B. Colvin, J. C. Madsen, A. B. Cosimi, T. Kawai, G. Benichou

研究成果: Article

27 引用 (Scopus)

抄録

Tolerance of allografts achieved in mice via stable mixed hematopoietic chimerism relies essentially on continuous elimination of developing alloreactive T cells in the thymus (central deletion). Conversely, while only transient mixed chimerism is observed in nonhuman primates and patients, it is sufficient to ensure tolerance of kidney allografts. In this setting, it is likely that tolerance depends on peripheral regulatory mechanisms rather than thymic deletion. This implies that, in primates, upsetting the balance between inflammatory and regulatory alloimmunity could abolish tolerance and trigger the rejection of previously accepted renal allografts. In this study, six monkeys that were treated with a mixed chimerism protocol and had accepted a kidney allograft for periods of 1-10 years after withdrawal of immunosuppression received subcutaneous injections of IL-2 cytokine (0.6-3 × 106 IU/m2). This resulted in rapid rejection of previously tolerated renal transplants and was associated with an expansion and reactivation of alloreactive pro-inflammatory memory T cells in the host's lymphoid organs and in the graft. This phenomenon was prevented by anti-CD8 antibody treatment. Finally, this process was reversible in that cessation of IL-2 administration aborted the rejection process and restored normal kidney graft function. Low dose injections of IL-2 break tolerance of kidney allografts induced via transient mixed hematopoietic chimerism in nonhuman primates.

元の言語English
ページ(範囲)3055-3066
ページ数12
ジャーナルAmerican Journal of Transplantation
15
発行部数12
DOI
出版物ステータスPublished - 2015 12 1
外部発表Yes

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Transplantation Tolerance
Chimerism
Interleukin-2
Haplorhini
Kidney
Injections
Primates
Transplants
Allografts
T-Lymphocytes
Subcutaneous Injections
Immunosuppression
Thymus Gland
Anti-Idiotypic Antibodies
Cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

これを引用

Yamada, Y., Nadazdin, O., Boskovic, S., Lee, S., Zorn, E., Smith, R. N., ... Benichou, G. (2015). Repeated injections of IL-2 break renal allograft tolerance induced via mixed hematopoietic chimerism in monkeys. American Journal of Transplantation, 15(12), 3055-3066. https://doi.org/10.1111/ajt.13382

Repeated injections of IL-2 break renal allograft tolerance induced via mixed hematopoietic chimerism in monkeys. / Yamada, Y.; Nadazdin, O.; Boskovic, S.; Lee, S.; Zorn, E.; Smith, R. N.; Colvin, R. B.; Madsen, J. C.; Cosimi, A. B.; Kawai, T.; Benichou, G.

:: American Journal of Transplantation, 巻 15, 番号 12, 01.12.2015, p. 3055-3066.

研究成果: Article

Yamada, Y, Nadazdin, O, Boskovic, S, Lee, S, Zorn, E, Smith, RN, Colvin, RB, Madsen, JC, Cosimi, AB, Kawai, T & Benichou, G 2015, 'Repeated injections of IL-2 break renal allograft tolerance induced via mixed hematopoietic chimerism in monkeys', American Journal of Transplantation, 巻. 15, 番号 12, pp. 3055-3066. https://doi.org/10.1111/ajt.13382
Yamada, Y. ; Nadazdin, O. ; Boskovic, S. ; Lee, S. ; Zorn, E. ; Smith, R. N. ; Colvin, R. B. ; Madsen, J. C. ; Cosimi, A. B. ; Kawai, T. ; Benichou, G. / Repeated injections of IL-2 break renal allograft tolerance induced via mixed hematopoietic chimerism in monkeys. :: American Journal of Transplantation. 2015 ; 巻 15, 番号 12. pp. 3055-3066.
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AU - Lee, S.

AU - Zorn, E.

AU - Smith, R. N.

AU - Colvin, R. B.

AU - Madsen, J. C.

AU - Cosimi, A. B.

AU - Kawai, T.

AU - Benichou, G.

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