BACKGROUND: Data on how different immunosuppressive drugs affect cytomegalovirus (CMV)-specific T-cell responses may help guide more rational modification of immunosuppression in patients with CMV replication. We assessed the in vitro effects of individual standard and novel immunosuppressive drugs on a broad range of CMV-specific T-cell responses. METHODS: Peripheral blood mononuclear cells from healthy CMV-seropositive donors were preincubated with serial dilutions of tacrolimus, mycophenolate (MPA), sirolimus, tofacitinib, and belatacept. CMV-pp65 or CMV-pp72 peptide pools were used for stimulation. CMV-specific cytokine (Th1 and Th2) and chemokine responses were determined (a total of 5400 measurements). P<0.01 was set as significant. RESULTS: After CMV stimulation, dose-dependent suppression of Th1, Th2, and chemokines was seen, but significant differences between drugs were present. For example, tacrolimus was more potent in inhibiting CMV-specific Th1 cytokines versus Th2, whereas MPA preferentially inhibited Th2 cytokines. In a comparison of the relative potency of each drug at different dosing ranges, tacrolimus had the strongest Th1 inhibitory effect (median inhibition of interferon-γ at 97.5%; P=0.004-0.008) followed by sirolimus (median inhibition at 82.4%). The remaining agents (MPA, belatacept, and tofacitinib) had less apparent dose-dependent effects on interferon-γ (belatacept median inhibition at 21.5%; P=0.004 vs. tacrolimus). CONCLUSION: Immunosuppression-specific and dose-dependent reductions in CMV-specific cytokine release were observed with significant differences in Th1 versus Th2 profiles and in relative potency of the drugs.
BACKGROUND: Data on how different immunosuppressive drugs affect cytomegalovirus (CMV)-specific T-cell responses may help guide more rational modification of immunosuppression in patients with CMV replication. We assessed the in vitro effects of individual standard and novel immunosuppressive drugs on a broad range of CMV-specific T-cell responses. METHODS: Peripheral blood mononuclear cells from healthy CMV-seropositive donors were preincubated with serial dilutions of tacrolimus, mycophenolate (MPA), sirolimus, tofacitinib, and belatacept. CMV-pp65 or CMV-pp72 peptide pools were used for stimulation. CMV-specific cytokine (Th1 and Th2) and chemokine responses were determined (a total of 5400 measurements). P<0.01 was set as significant. RESULTS: After CMV stimulation, dose-dependent suppression of Th1, Th2, and chemokines was seen, but significant differences between drugs were present. For example, tacrolimus was more potent in inhibiting CMV-specific Th1 cytokines versus Th2, whereas MPA preferentially inhibited Th2 cytokines. In a comparison of the relative potency of each drug at different dosing ranges, tacrolimus had the strongest Th1 inhibitory effect (median inhibition of interferon-γ at 97.5%; P=0.004-0.008) followed by sirolimus (median inhibition at 82.4%). The remaining agents (MPA, belatacept, and tofacitinib) had less apparent dose-dependent effects on interferon-γ (belatacept median inhibition at 21.5%; P=0.004 vs. tacrolimus). CONCLUSION: Immunosuppression-specific and dose-dependent reductions in CMV-specific cytokine release were observed with significant differences in Th1 versus Th2 profiles and in relative potency of the drugs.
Authors: Sahra Pajenda; Sebastian Kapps; Daniela Gerges; Gregor Hoermann; Ludwig Wagner; Nina Buchtele; Barbara Geist; Robert Strassl; Alice Schmidt; Wolfgang Winnicki Journal: BMC Nephrol Date: 2021-05-08 Impact factor: 2.388
Authors: Elisa Piscianz; Erica Valencic; Eva Cuzzoni; Sara De Iudicibus; Elisa De Lorenzo; Giuliana Decorti; Alberto Tommasini Journal: PLoS One Date: 2014-01-09 Impact factor: 3.240
Authors: F Ratzinger; H Haslacher; W Poeppl; G Hoermann; J J Kovarik; S Jutz; P Steinberger; H Burgmann; W F Pickl; K G Schmetterer Journal: Sci Rep Date: 2014-12-11 Impact factor: 4.379
Authors: Giulio Cossu; Stefano C Previtali; Sara Napolitano; Maria Pia Cicalese; Francesco Saverio Tedesco; Francesca Nicastro; Maddalena Noviello; Urmas Roostalu; Maria Grazia Natali Sora; Marina Scarlato; Maurizio De Pellegrin; Claudia Godi; Serena Giuliani; Francesca Ciotti; Rossana Tonlorenzi; Isabella Lorenzetti; Cristina Rivellini; Sara Benedetti; Roberto Gatti; Sarah Marktel; Benedetta Mazzi; Andrea Tettamanti; Martina Ragazzi; Maria Adele Imro; Giuseppina Marano; Alessandro Ambrosi; Rossana Fiori; Maria Pia Sormani; Chiara Bonini; Massimo Venturini; Letterio S Politi; Yvan Torrente; Fabio Ciceri Journal: EMBO Mol Med Date: 2015-12 Impact factor: 12.137