The effect of ATG on cytokine and cytotoxic T-lymphocyte gene expression in renal allograft recipients during the early post-transplant period.
BACKGROUND
Despite the long history of ATG use, the exact in vivo mechanism of action remains unclear. In the present study, we analyzed the effect of ATG-induction therapy on expression of 10 immunologically relevant genes in the early post-transplant period.


METHODS
Eight renal allograft recipients received post-transplant prophylactic ATG treatment on 10 consecutive days and an additional three patients received treatment on 5, 6, or 7 consecutive days, respectively. Gene expression was measured at the beginning and the end of therapy and normalized to a control gene using Taqman real-time PCR methodology. Results were compared with those of matched control patients. No patients were diagnosed with rejection.


RESULTS
ATG-treated patients showed decreases in the expression of cytotoxic T cell genes perforin (-56%, p = 0.03) and granzyme B (-45%, p = 0.01) and cytokine gene IFN-gamma (-75%, p = 0.005), and significant increases in the expression of cytokine genes IL-7 (550%, p = 0.04), IL-10 (275%, p = 0.01), IL-15 (417%, p = 0.03), TNF-alpha (615%, p = 0.01), and TGF-beta (235%, p = 0.02). No significant changes were observed in the control group, with the exception of a decrease in IL-10 expression (-42%, p = 0.01). There were no significant changes in IL-12 or Fas-L expression in either group.


CONCLUSIONS
ATG-induced decreases in the expression of IFN-gamma, perforin, and granzyme B and increases in IL-10 and TGF-beta might be considered beneficial to the recipient, whereas increases in the expression of IL-7, IL-15, and TNF-alpha genes might be involved in immunological processes not effected by ATG that may harm the transplant in the long term.
Simon
Tania
T
Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
Opelz
Gerhard
G
Weimer
Rolf
R
Wiesel
Manfred
M
Feustel
Andreas
A
Ott
Ralf C
RC
Süsal
Caner
C
D000328:Adult; D000961:Antilymphocyte Serum / Q000494:pharmacology*; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D016133:Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*
D000961:Antilymphocyte Serum; D016207:Cytokines