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Metastable tolerance to rhesus monkey renal transplants is correlated with allograft TGF-beta 1+CD4+ T regulatory cell infiltrates.

Publication ,  Journal Article
Torrealba, JR; Katayama, M; Fechner, JH; Jankowska-Gan, E; Kusaka, S; Xu, Q; Schultz, JM; Oberley, TD; Hu, H; Hamawy, MM; Jonker, M; Wubben, J ...
Published in: J Immunol
May 1, 2004

Approaches that prevent acute rejection of renal transplants in a rhesus monkey model were studied to determine a common mechanism of acceptance. After withdrawal of immunosuppression, all 14 monkeys retained normal allograft function for >6 mo. Of these, nine rejected their renal allograft during the study, and five maintained normal function throughout the study period. The appearance of TGF-beta 1(+) interstitial mononuclear cells in the graft coincided with a nonrejection histology, whereas the absence/disappearance of these cells was observed with the onset of rejection. Analysis with a variety of TGF-beta 1-reactive Abs indicated that the tolerance-associated infiltrates expressed the large latent complex form of TGF-beta 1. Peripheral leukocytes from rejecting monkeys lacking TGF-beta 1(+) allograft infiltrates responded strongly to donor Ags in delayed-type hypersensitivity trans-vivo assays. In contrast, allograft acceptors with TGF-beta 1(+) infiltrates demonstrated a much weaker peripheral delayed-type hypersensitivity response to donor alloantigens (p < 0.01 vs rejectors), which could be restored by Abs that either neutralized active TGF-beta 1 or blocked its conversion from latent to active form. Anti-IL-10 Abs had no restorative effect. Accepted allografts had CD8(+) and CD4(+) interstitial T cell infiltrates, but only the CD4(+) subset included cells costaining for TGF-beta 1. Our data support the hypothesis that the recruitment of CD4(+) T regulatory cells to the allograft interstitium is a final common pathway for metastable renal transplant tolerance in a non-human primate model.

Duke Scholars

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Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

May 1, 2004

Volume

172

Issue

9

Start / End Page

5753 / 5764

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Transplantation Tolerance
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta
  • T-Lymphocyte Subsets
  • Mice, SCID
  • Mice
  • Macaca mulatta
  • Leukocytes, Mononuclear
  • Kidney Transplantation
 

Citation

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Torrealba, J. R., Katayama, M., Fechner, J. H., Jankowska-Gan, E., Kusaka, S., Xu, Q., … Knechtle, S. J. (2004). Metastable tolerance to rhesus monkey renal transplants is correlated with allograft TGF-beta 1+CD4+ T regulatory cell infiltrates. J Immunol, 172(9), 5753–5764. https://doi.org/10.4049/jimmunol.172.9.5753
Torrealba, Jose R., Masaaki Katayama, John H. Fechner, Ewa Jankowska-Gan, Satoshi Kusaka, Qingyong Xu, Jacqueline M. Schultz, et al. “Metastable tolerance to rhesus monkey renal transplants is correlated with allograft TGF-beta 1+CD4+ T regulatory cell infiltrates.J Immunol 172, no. 9 (May 1, 2004): 5753–64. https://doi.org/10.4049/jimmunol.172.9.5753.
Torrealba JR, Katayama M, Fechner JH, Jankowska-Gan E, Kusaka S, Xu Q, et al. Metastable tolerance to rhesus monkey renal transplants is correlated with allograft TGF-beta 1+CD4+ T regulatory cell infiltrates. J Immunol. 2004 May 1;172(9):5753–64.
Torrealba, Jose R., et al. “Metastable tolerance to rhesus monkey renal transplants is correlated with allograft TGF-beta 1+CD4+ T regulatory cell infiltrates.J Immunol, vol. 172, no. 9, May 2004, pp. 5753–64. Pubmed, doi:10.4049/jimmunol.172.9.5753.
Torrealba JR, Katayama M, Fechner JH, Jankowska-Gan E, Kusaka S, Xu Q, Schultz JM, Oberley TD, Hu H, Hamawy MM, Jonker M, Wubben J, Doxiadis G, Bontrop R, Burlingham WJ, Knechtle SJ. Metastable tolerance to rhesus monkey renal transplants is correlated with allograft TGF-beta 1+CD4+ T regulatory cell infiltrates. J Immunol. 2004 May 1;172(9):5753–5764.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

May 1, 2004

Volume

172

Issue

9

Start / End Page

5753 / 5764

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Transplantation Tolerance
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta
  • T-Lymphocyte Subsets
  • Mice, SCID
  • Mice
  • Macaca mulatta
  • Leukocytes, Mononuclear
  • Kidney Transplantation