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. Conclusion: 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.