BACKGROUND: Although immunosuppression withdrawal in kidney recipients usually leads to rejection, in some patients it does not, leading to a state of clinical operational tolerance. METHODS: We compared these highly contrasted situations by analyzing blood cell phenotype and transcriptional patterns in drug-free spontaneously tolerant kidney recipients, recipients with chronic rejection, recipients with stable graft function under standard or minimal immunosuppression and healthy individuals RESULTS: The blood cell phenotype of clinically tolerant patients did not differ from that of healthy individuals. In contrast, recipients with chronic rejection had significantly less CD25hiCD4+T cells and lower levels of FOXP3 transcripts compared with clinically tolerant recipients. Patients with chronic rejection also displayed CD25-CD4+T cells expressing NKG2D+CD94+ and CD57+CD27-CD28- cytotoxic-associated markers (P<0.05). CONCLUSION: These data show that whereas clinically tolerant recipients displayed normal levels of CD25hiCD4+T cells and FOXP3 transcripts, chronic rejection is associated with a decrease in CD25hiCD4+T cells and FOXP3 transcripts, suggesting that clinically "operational tolerance" may be due to a maintained phenomenon of natural tolerance that is lacking in patients with chronic rejection.
BACKGROUND: Although immunosuppression withdrawal in kidney recipients usually leads to rejection, in some patients it does not, leading to a state of clinical operational tolerance. METHODS: We compared these highly contrasted situations by analyzing blood cell phenotype and transcriptional patterns in drug-free spontaneously tolerant kidney recipients, recipients with chronic rejection, recipients with stable graft function under standard or minimal immunosuppression and healthy individuals RESULTS: The blood cell phenotype of clinically tolerant patients did not differ from that of healthy individuals. In contrast, recipients with chronic rejection had significantly less CD25hiCD4+T cells and lower levels of FOXP3 transcripts compared with clinically tolerant recipients. Patients with chronic rejection also displayed CD25-CD4+T cells expressing NKG2D+CD94+ and CD57+CD27-CD28- cytotoxic-associated markers (P<0.05). CONCLUSION: These data show that whereas clinically tolerant recipients displayed normal levels of CD25hiCD4+T cells and FOXP3 transcripts, chronic rejection is associated with a decrease in CD25hiCD4+T cells and FOXP3 transcripts, suggesting that clinically "operational tolerance" may be due to a maintained phenomenon of natural tolerance that is lacking in patients with chronic rejection.
Authors: Richard Danger; Annaïck Pallier; Magali Giral; Marc Martínez-Llordella; Juan José Lozano; Nicolas Degauque; Alberto Sanchez-Fueyo; Jean-Paul Soulillou; Sophie Brouard Journal: J Am Soc Nephrol Date: 2012-01-26 Impact factor: 10.121
Authors: Fabrice Porcheray; Julie DeVito; Beow Y Yeap; Lijuan Xue; Ian Dargon; Rosemary Paine; Timothy C Girouard; Susan L Saidman; Robert B Colvin; Waichi Wong; Emmanuel Zorn Journal: Transplantation Date: 2010-05-27 Impact factor: 4.939
Authors: Pervinder Sagoo; Esperanza Perucha; Birgit Sawitzki; Stefan Tomiuk; David A Stephens; Patrick Miqueu; Stephanie Chapman; Ligia Craciun; Ruhena Sergeant; Sophie Brouard; Flavia Rovis; Elvira Jimenez; Amany Ballow; Magali Giral; Irene Rebollo-Mesa; Alain Le Moine; Cecile Braudeau; Rachel Hilton; Bernhard Gerstmayer; Katarzyna Bourcier; Adnan Sharif; Magdalena Krajewska; Graham M Lord; Ian Roberts; Michel Goldman; Kathryn J Wood; Kenneth Newell; Vicki Seyfert-Margolis; Anthony N Warrens; Uwe Janssen; Hans-Dieter Volk; Jean-Paul Soulillou; Maria P Hernandez-Fuentes; Robert I Lechler Journal: J Clin Invest Date: 2010-05-24 Impact factor: 14.808
Authors: Laure Vallotton; Karine Hadaya; Jean-Pierre Venetz; Leo H Buehler; Donatella Ciuffreda; Ghaleb Nseir; Laura Codarri; Jean Villard; Giuseppe Pantaleo; Manuel Pascual Journal: Clin J Am Soc Nephrol Date: 2011-07-14 Impact factor: 8.237
Authors: Ran Tao; Edwin F de Zoeten; Engin Ozkaynak; Liqing Wang; Bin Li; Mark I Greene; Andrew D Wells; Wayne W Hancock Journal: Curr Opin Immunol Date: 2007-08-24 Impact factor: 7.486