2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by SHIMIZU, A. Articles by COLVIN, R. B. Search for Related Content PubMed PubMed Citation Articles by SHIMIZU, A. Articles by COLVIN, R. B.

Acceptance Reaction: Intragraft Events Associated with Tolerance to Renal Allografts in Miniature Swine

AKIRA SHIMIZU^*,§, KAZUHIKO YAMADA, SHANE M. MEEHAN, DAVID H. SACHS and ROBERT B. COLVIN^*

^* Department of Pathology, Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts
Department of Transplantation, Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts
Department of Pathology, University of Chicago, Chicago, Illinois
^§ Department of Pathology, Nippon Medical School, Tokyo, Japan.

Correspondence to Dr. Robert B. Colvin, Department of Pathology, Massachusetts General Hospital, 55 Fruit Street (WRN 225), Boston, MA 02114; Phone: 617-726-2966; Fax: 617-726-7533; E-mail: colvin{at}helix.mgh.harvard.edu

Abstract. Inbred miniature swine that are treated for 12 d with a high dose of cyclosporin A develop tolerance to MHC class II matched, class I-mismatched renal allografts. The aim of this study was to clarify the intrarenal allograft events associated with the development of tolerance in this protocol. Morphologic and immunologic studies were performed in serial biopsies from accepting grafts after 12 d of cyclosporin A treatment (n = 4) and were compared with those from untreated control rejecting grafts (n = 4). In accepting grafts with stable function, a transient interstitial infiltrate developed. The cellular infiltrate had many similarities to that in rejecting grafts; both had T cells and macrophages, similar proportions of T-cell subsets, and a similar frequency of in situ nick end labeling (TUNEL)+ apoptotic infiltrating cells. However, the cellular infiltrate in the acceptance reaction was distinguished by less T-cell activation (interleukin-2 receptor+), less proliferation (proliferating cell nuclear antigen+) of infiltrating cells, and less graft cell apoptosis in arteries, tubules, glomeruli, and peritubular capillaries. Thereafter, the infiltrate in the accepting grafts progressively resolved with decreased cell proliferation, activation, and apoptotic graft parenchymal cell injury, but the high frequency of apoptosis persisted in graft-infiltrating cells. In parallel to the intragraft events, donor-specific unresponsiveness developed as assessed by cell-mediated cytotoxicity by blood mononuclear cells in vitro. In conclusion, the acceptance reaction in transplanted grafts is characterized by progressive resolution of T-cell proliferation and activation and of cell-mediated graft injury, as well as prolonged T-cell apoptosis. These intragraft events suggest that both T-cell anergy and T-cell deletion occur in the graft during the development of tolerance. Some of the described immunopathologic findings (activation, proliferation, apoptosis) may be useful in distinguishing acceptance from rejection, as well as in predicting later graft acceptance in tolerance induction protocols.

This article has been cited by other articles:

				J.-F. Cailhier, I. Sirois, P. Laplante, S. Lepage, M.-A. Raymond, N. Brassard, A. Prat, R. V. Iozzo, A. V. Pshezhetsky, and M.-J. Hebert Caspase-3 Activation Triggers Extracellular Cathepsin L Release and Endorepellin Proteolysis J. Biol. Chem., October 3, 2008; 283(40): 27220 - 27229. [Abstract] [Full Text] [PDF]

				W. Harmon, K. Meyers, J. Ingelfinger, R. McDonald, M. McIntosh, M. Ho, L. Spaneas, J. A. Palmer, M. Hawk, C. Geehan, et al. Safety and Efficacy of a Calcineurin Inhibitor Avoidance Regimen in Pediatric Renal Transplantation J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1735 - 1745. [Abstract] [Full Text] [PDF]

				S. Shishido, H. Asanuma, H. Nakai, Y. Mori, H. Satoh, I. Kamimaki, H. Hataya, M. Ikeda, M. Honda, and A. Hasegawa The Impact of Repeated Subclinical Acute Rejection on the Progression of Chronic Allograft Nephropathy J. Am. Soc. Nephrol., April 1, 2003; 14(4): 1046 - 1052. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673