Regulatory, effector, and cytotoxic T cell profiles in long-term kidney transplant patients.
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.
INSERM, U643, Institut de Transplantation et de Recherche en Transplantation, Centre Hospitalier Universitaire de Nantes, Nantes, France.
Joanna
J
Ashton-Chess
Emilie
E
Dugast
Robert B
RB
Colvin
Magali
M
Giral
Yohann
Y
Foucher
Anne
A
Moreau
Karine
K
Renaudin
Christophe
C
Braud
Anne
A
Devys
Sophie
S
Brouard
Jean-Paul
JP
Soulillou
D015415:Biomarkers / Q000032:analysis; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000235:genetics; D006084:Graft Rejection / Q000175:diagnosis / Q000473:pathology; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology
D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger