Immunomodulation by intrathymic injection of donor leukocytes in rhesus monkeys

Margreet Jonker, Yvon Van Den Hout, Riet C. Noort, Minke F J Versteeg-Van Der Voort Maarschalk, Frans H J Claas, Fokko J. Vd Woude, Daan Hollander, Norberto Perico, Giuseppe Remuzzi

Research output: Contribution to journalArticle

Abstract

Background. Several studies have demonstrated that intrathymic injection of donor cells into adult rodents can result in long-term allograft survival. The rationale for using the intrathymic route of donor cell administration is that in the thymic environment immature T cells are educated to discriminate between self and non-self antigens. The validity of this approach was tested in non-human primates. Methods. The effect of the intrathymic injection of allogeneic donor cells was investigated in rhesus monkeys and compared with IV and intracutaneous administration of donor cells. Intrathymic injections were carried out without and with antithymocyte globulin. All animals received subsequently an allogeneic skin graft of the same donor and no immunosuppression post transplantation. Results. Skin graft survival was slightly shorter in animals treated with IC donor cell injections (mean survival time [MST]=8.9±0.52) than untreated control animals (MST=10.0±0.44), indicating that this route caused sensitisation. Intravenous donor cell injection showed prolongation of graft survival times (MST=11.6±1.69). Intrathymic donor cell injection resulted in a graft survival of 9.2 ± 1.44 days although addition of antithymocyte globulin slightly prolonged graft survival to 10.3±2.84 (not significant). Whereas the cellular responses after intrathymic and intravenous donor cell injections increased, antithymocyte globulin treated animals did not show an increased cellular response. Recipients of intrathymic donor cells showed a significantly decreased humoral anti-donor response as compared to other groups. Conclusions. Donor cell pretreatment alters the subsequent response to an allogeneic skin graft in monkeys and is dependent on the route of donor cell administration. This is also reflected in the alloantibody response and the in vitro cellular reactivity. Intrathymic administration of donor cells does not lead to prolonged skin graft acceptance.

Original languageEnglish
Pages (from-to)1432-1436
Number of pages5
JournalTransplantation
Volume72
Issue number8
Publication statusPublished - Oct 27 2001

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Immunomodulation
Macaca mulatta
Leukocytes
Injections
Graft Survival
Antilymphocyte Serum
Skin
Transplants
Isoantibodies
Immunosuppression
Primates
Haplorhini
Allografts
Rodentia
Transplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Jonker, M., Van Den Hout, Y., Noort, R. C., Versteeg-Van Der Voort Maarschalk, M. F. J., Claas, F. H. J., Vd Woude, F. J., ... Remuzzi, G. (2001). Immunomodulation by intrathymic injection of donor leukocytes in rhesus monkeys. Transplantation, 72(8), 1432-1436.

Immunomodulation by intrathymic injection of donor leukocytes in rhesus monkeys. / Jonker, Margreet; Van Den Hout, Yvon; Noort, Riet C.; Versteeg-Van Der Voort Maarschalk, Minke F J; Claas, Frans H J; Vd Woude, Fokko J.; Hollander, Daan; Perico, Norberto; Remuzzi, Giuseppe.

In: Transplantation, Vol. 72, No. 8, 27.10.2001, p. 1432-1436.

Research output: Contribution to journalArticle

Jonker, M, Van Den Hout, Y, Noort, RC, Versteeg-Van Der Voort Maarschalk, MFJ, Claas, FHJ, Vd Woude, FJ, Hollander, D, Perico, N & Remuzzi, G 2001, 'Immunomodulation by intrathymic injection of donor leukocytes in rhesus monkeys', Transplantation, vol. 72, no. 8, pp. 1432-1436.
Jonker M, Van Den Hout Y, Noort RC, Versteeg-Van Der Voort Maarschalk MFJ, Claas FHJ, Vd Woude FJ et al. Immunomodulation by intrathymic injection of donor leukocytes in rhesus monkeys. Transplantation. 2001 Oct 27;72(8):1432-1436.
Jonker, Margreet ; Van Den Hout, Yvon ; Noort, Riet C. ; Versteeg-Van Der Voort Maarschalk, Minke F J ; Claas, Frans H J ; Vd Woude, Fokko J. ; Hollander, Daan ; Perico, Norberto ; Remuzzi, Giuseppe. / Immunomodulation by intrathymic injection of donor leukocytes in rhesus monkeys. In: Transplantation. 2001 ; Vol. 72, No. 8. pp. 1432-1436.
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abstract = "Background. Several studies have demonstrated that intrathymic injection of donor cells into adult rodents can result in long-term allograft survival. The rationale for using the intrathymic route of donor cell administration is that in the thymic environment immature T cells are educated to discriminate between self and non-self antigens. The validity of this approach was tested in non-human primates. Methods. The effect of the intrathymic injection of allogeneic donor cells was investigated in rhesus monkeys and compared with IV and intracutaneous administration of donor cells. Intrathymic injections were carried out without and with antithymocyte globulin. All animals received subsequently an allogeneic skin graft of the same donor and no immunosuppression post transplantation. Results. Skin graft survival was slightly shorter in animals treated with IC donor cell injections (mean survival time [MST]=8.9±0.52) than untreated control animals (MST=10.0±0.44), indicating that this route caused sensitisation. Intravenous donor cell injection showed prolongation of graft survival times (MST=11.6±1.69). Intrathymic donor cell injection resulted in a graft survival of 9.2 ± 1.44 days although addition of antithymocyte globulin slightly prolonged graft survival to 10.3±2.84 (not significant). Whereas the cellular responses after intrathymic and intravenous donor cell injections increased, antithymocyte globulin treated animals did not show an increased cellular response. Recipients of intrathymic donor cells showed a significantly decreased humoral anti-donor response as compared to other groups. Conclusions. Donor cell pretreatment alters the subsequent response to an allogeneic skin graft in monkeys and is dependent on the route of donor cell administration. This is also reflected in the alloantibody response and the in vitro cellular reactivity. Intrathymic administration of donor cells does not lead to prolonged skin graft acceptance.",
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AU - Jonker, Margreet

AU - Van Den Hout, Yvon

AU - Noort, Riet C.

AU - Versteeg-Van Der Voort Maarschalk, Minke F J

AU - Claas, Frans H J

AU - Vd Woude, Fokko J.

AU - Hollander, Daan

AU - Perico, Norberto

AU - Remuzzi, Giuseppe

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N2 - Background. Several studies have demonstrated that intrathymic injection of donor cells into adult rodents can result in long-term allograft survival. The rationale for using the intrathymic route of donor cell administration is that in the thymic environment immature T cells are educated to discriminate between self and non-self antigens. The validity of this approach was tested in non-human primates. Methods. The effect of the intrathymic injection of allogeneic donor cells was investigated in rhesus monkeys and compared with IV and intracutaneous administration of donor cells. Intrathymic injections were carried out without and with antithymocyte globulin. All animals received subsequently an allogeneic skin graft of the same donor and no immunosuppression post transplantation. Results. Skin graft survival was slightly shorter in animals treated with IC donor cell injections (mean survival time [MST]=8.9±0.52) than untreated control animals (MST=10.0±0.44), indicating that this route caused sensitisation. Intravenous donor cell injection showed prolongation of graft survival times (MST=11.6±1.69). Intrathymic donor cell injection resulted in a graft survival of 9.2 ± 1.44 days although addition of antithymocyte globulin slightly prolonged graft survival to 10.3±2.84 (not significant). Whereas the cellular responses after intrathymic and intravenous donor cell injections increased, antithymocyte globulin treated animals did not show an increased cellular response. Recipients of intrathymic donor cells showed a significantly decreased humoral anti-donor response as compared to other groups. Conclusions. Donor cell pretreatment alters the subsequent response to an allogeneic skin graft in monkeys and is dependent on the route of donor cell administration. This is also reflected in the alloantibody response and the in vitro cellular reactivity. Intrathymic administration of donor cells does not lead to prolonged skin graft acceptance.

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