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) All Versions of this Article: ASN.2005020178v1 17/1/294    most recent 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 Baeten, D. Articles by Soulillou, J.-P. Search for Related Content PubMed PubMed Citation Articles by Baeten, D. Articles by Soulillou, J.-P. Related Collections Related Articles

Phenotypically and Functionally Distinct CD8⁺ Lymphocyte Populations in Long-Term Drug-Free Tolerance and Chronic Rejection in Human Kidney Graft Recipients

Dominique Baeten^*,, Stéphanie Louis^*, Christophe Braud^*, Cécile Braudeau^*, Caroline Ballet^*, Frédéric Moizant^*, Annaik Pallier^*, Magali Giral^*, Sophie Brouard^* and Jean-Paul Soulillou^*

^* Institut National de la Santé Et de la Recherche Médicale (INSERM), Unité 643: "Immunointervention dans les Allo- et Xénotransplantations," and Institut de Transplantation Et de Recherche en Transplantation (ITERT), Nantes, France; and Department of Clinical Immunology and Rheumatology, Amsterdam Medical Center, Amsterdam, The Netherlands

Address correspondence to: Prof. Dr. Jean-Paul Soulillou, INSERM U643, CHU Hôtel-Dieu, 30 Bd Jean Monnet, 44093 Nantes Cedex 01, France. Phone: +33-2-240-08-74-70; Fax: +33-2-240-08-74-77; E-mail: jean-paul.soulillou{at}univ-nantes.fr

Received for publication February 16, 2005. Accepted for publication October 17, 2005.

A substantial proportion of long-term kidney graft recipients, including those with a stable renal function in the absence of immunosuppressive therapy, present a skewed T cell receptor (TCR) V chain usage, essentially in the CD8⁺ subset. This study analyzed in more detail phenotypical and functional alterations of CD8⁺ lymphocytes in drug-free tolerant patients (DF-Tol) compared with recipients with chronic rejection (CR). Phenotyping revealed a significant increase in central memory and a decrease in effector CD8⁺ lymphocytes in DF-Tol versus CR. The expression of CD28⁺ and CD27⁺ on these effector cells was significantly decreased in CR. These profiles were stable over time and independent of treatment. Functionally, the CD8⁺CD28^– lymphocytes were less sensitive to apoptosis than their CD8⁺CD28⁺ counterparts, without differences in polyclonal proliferation. The CD8⁺CD28^– cells did not express GITR and FoxP3 but were characterized by high levels of preformed perforin and granzyme A, pointing toward a cytotoxic rather than a suppressor function. CD8⁺CD28^– lymphocytes did not show antigen-specific degranulation when co-cultured with targets that bear donor HLA class I antigens, suggesting that the cytotoxicity is directed either to other determinants of the graft or to nongraft epitopes. Of interest, CD8⁺ cells from DF-Tol displayed the same profile as healthy individuals, indicating an increase in CD8⁺CD28^– effector lymphocytes in CR rather than a decrease in DF-Tol. CD8⁺ lymphocytes from stable kidney recipients under conventional maintenance immunosuppression displayed a mixed profile, independent of treatment and time of sampling. Taken collectively, these data show a strong cytotoxicity-associated CD8⁺CD28^– signature in CR and suggest a suppression of pathologic cytotoxicity in DF-Tol. Further prospective studies should assess whether serial CD8⁺ phenotyping may help to identify patients who are at risk for CR when immunosuppression is tapered.

Related Articles

Protocol Transplant Biopsies: Are They Really Needed?

Alan Wilkinson
Clin. J. Am. Soc. Nephrol. 2006 1: 130-137. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				P. Trzonkowski, A. Debska-Slizien, A. Mysliwski, and B. Rutkowski Treatment with recombinant human erythropoietin is associated with rejuvenation of CD8+ T cell compartment in chronic renal failure patients Nephrol. Dial. Transplant., November 1, 2007; 22(11): 3221 - 3227. [Abstract] [Full Text] [PDF]

				S. Brouard, E. Mansfield, C. Braud, L. Li, M. Giral, S.-c. Hsieh, D. Baeten, M. Zhang, J. Ashton-Chess, C. Braudeau, et al. Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance PNAS, September 25, 2007; 104(39): 15448 - 15453. [Abstract] [Full Text] [PDF]

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