BACKGROUND: Regulatory FOXP3+ T cells control immune responses of effector T cells. However, whether these cells regulate antidonor responses in the graft of cardiac allograft patients is unknown. Therefore, we analyzed the gene expression profiles of regulatory and effector T-cell markers during immunological quiescence and acute rejection. METHODS: Quantitative real-time polymerase chain reaction was used to analyze mRNA expression levels in time-zero specimens (n=24) and endomyocardial biopsies (EMB; n=72) of cardiac allograft patients who remained free from rejection (nonrejectors; n=12) and patients with at least one histologically proven acute rejection episode (rejectors; International Society for Heart and Lung Transplantation [ISHLT] rejection grade>2; n=12). RESULTS: For all analyzed regulatory and effector T-cell markers, mRNA expression levels were increased in biopsies taken after heart transplantation compared with those in time-zero specimens. Posttransplantation, the FOXP3 mRNA levels were higher in EMB assigned to a higher ISHLT rejection grade than the biopsies with grade 0: the highest mRNA levels were detected in the rejection biopsies (rejection grade>2; P=0.003). In addition, the mRNA levels of CD25, glucocorticoid-induced TNF receptor family-related gene, cytotoxic T lymphocyte-associated antigen 4, interleukin-2, and granzyme B were also significantly higher in rejecting EMB than in nonrejecting EMB (rejection grade<or=2). This increase in expression levels in relation to the histological rejection grade was only observed in patients who developed an acute rejection episode; the mRNA levels of nonrejectors remained stable irrespective of ISHLT rejection grade. CONCLUSIONS: These observations suggest that, after clinical heart transplantation, FOXP3+ T cells do not prevent acute rejection, but rather are a response to antidonor effector T-cell activity.
BACKGROUND: Regulatory FOXP3+ T cells control immune responses of effector T cells. However, whether these cells regulate antidonor responses in the graft of cardiac allograft patients is unknown. Therefore, we analyzed the gene expression profiles of regulatory and effector T-cell markers during immunological quiescence and acute rejection. METHODS: Quantitative real-time polymerase chain reaction was used to analyze mRNA expression levels in time-zero specimens (n=24) and endomyocardial biopsies (EMB; n=72) of cardiac allograft patients who remained free from rejection (nonrejectors; n=12) and patients with at least one histologically proven acute rejection episode (rejectors; International Society for Heart and Lung Transplantation [ISHLT] rejection grade>2; n=12). RESULTS: For all analyzed regulatory and effector T-cell markers, mRNA expression levels were increased in biopsies taken after heart transplantation compared with those in time-zero specimens. Posttransplantation, the FOXP3 mRNA levels were higher in EMB assigned to a higher ISHLT rejection grade than the biopsies with grade 0: the highest mRNA levels were detected in the rejection biopsies (rejection grade>2; P=0.003). In addition, the mRNA levels of CD25, glucocorticoid-induced TNF receptor family-related gene, cytotoxic T lymphocyte-associated antigen 4, interleukin-2, and granzyme B were also significantly higher in rejecting EMB than in nonrejecting EMB (rejection grade<or=2). This increase in expression levels in relation to the histological rejection grade was only observed in patients who developed an acute rejection episode; the mRNA levels of nonrejectors remained stable irrespective of ISHLT rejection grade. CONCLUSIONS: These observations suggest that, after clinical heart transplantation, FOXP3+ T cells do not prevent acute rejection, but rather are a response to antidonor effector T-cell activity.
Authors: Stephen P Cobbold; Elizabeth Adams; Claire A Farquhar; Kathleen F Nolan; Duncan Howie; Kathy O Lui; Paul J Fairchild; Andrew L Mellor; David Ron; Herman Waldmann Journal: Proc Natl Acad Sci U S A Date: 2009-06-30 Impact factor: 11.205
Authors: Robert P Carroll; David San Segundo; Kevin Hollowood; Teresa Marafioti; Taane G Clark; Paul N Harden; Kathryn J Wood Journal: J Am Soc Nephrol Date: 2010-01-28 Impact factor: 10.121
Authors: Yannick D Muller; Gang Mai; Philippe Morel; Véronique Serre-Beinier; Carmen Gonelle-Gispert; Gisella Puga Yung; Driss Ehirchiou; Jean-Christophe Wyss; Sinda Bigenzahn; Magali Irla; Christoph Heusser; Déla Golshayan; Jörg D Seebach; Thomas Wekerle; Leo H Bühler Journal: PLoS One Date: 2010-04-26 Impact factor: 3.240
Authors: Masato Fujiki; Carlos O Esquivel; Olivia M Martinez; Samuel Strober; Shinji Uemoto; Sheri M Krams Journal: Liver Transpl Date: 2010-02 Impact factor: 5.799