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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • May 2004

Published In

Volume / Issue

  • 172 / 9

Start / End Page

  • 5753 - 5764

PubMed ID

  • 15100322

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.172.9.5753

Language

  • eng