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Regulatory, Effector, and Cytotoxic T Cell Profiles in Long-Term Kidney Transplant Patients

Joanna Ashton-Chess^*, Emilie Dugast^*, Robert B. Colvin, Magali Giral^*, Yohann Foucher^*, Anne Moreau, Karine Renaudin, Christophe Braud^*, Anne Devys, Sophie Brouard^* and Jean-Paul Soulillou^*

^* INSERM, U643, Nantes, France; Institut de Transplantation et de Recherche en Transplantation, Centre Hospitalier Universitaire de Nantes, Nantes, France; Faculté de Médecine, Université de Nantes, Nantes, France; Department of Pathology, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts; Service d'Anatomie Pathologique, Centre Hospitalier Universitaire de Nantes, Nantes, France; and Etablissement Français du Sang, Nantes, France

Correspondence: Sophie Brouard or Jean-Paul Soulillou, ITERT/INSERM U643, CHU Hôtel Dieu, 30 Bd Jean Monnet, 44093 Nantes, Cedex 1, France. Phone: +33 240 08 74 10; Fax: +33 240 08 74 11; E-mail: sophie.brouard{at}university-nantes.fr; jean-paul.soulillou{at}university-nantes.fr

Received for publication April 23, 2008. Accepted for publication November 21, 2008.

Animal studies have suggested a potential role for regulatory T cells (Tregs) in allograft tolerance, but these FOXP3+ cells seem to be an inherent component of acute rejection (AR) in human recipients of renal transplants. The balance between regulatory cells and effector/cytotoxic cells may determine graft outcome; this balance has not been described for chronic allograft injury. We investigated the expression of key regulatory, effector, and cytotoxic transcripts (i.e., FOXP3, T-bet, and granzyme B, respectively) in the grafts and peripheral blood of long-term-surviving renal transplant patients. We found that, whereas neither intragraft nor peripheral blood FOXP3 or T-bet mRNA could distinguish between rejection and nonrejection status, granzyme B (GrzB) mRNA could: It was significantly increased in the graft and significantly decreased in the peripheral blood of patients with chronic antibody-mediated rejection (CAMR). Quantifying peripheral blood GrzB mRNA demonstrated potential to aid in the noninvasive diagnosis of CAMR. In summary, these data affirm GrzB as a marker not only for AR but also for CAMR. In addition, we identified several previously unreported clinical or demographic factors influencing regulatory/effector/cytotoxic profiles in the peripheral blood, highlighting the necessity to consider confounding variables when considering the use of potential biomarkers, such as FOXP3, for diagnosis or prognosis in kidney transplantation.

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673