Effector T cells (Th-) Regulatory T cells Treg Th17 Th1 Th2

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Effector T cells (Th-) Regulatory T cells Treg Th17 Th1 Th2 Supplemental Diglta Content 1 _ Figure 1 Effector T cells (Th-) a/ Regulatory T cells Treg Th17 Th1 Th2 FOXP3 RORgt Tbet GATA3 * ns ns ns ns ns *** *** *** ** *** *** TGFb IL17A IFNg IL4 ** ns ns ns *** *** ns *** *** *** ns *** IL10 IL21 TIM3 * ns * *** *** * *** *** ***

ns MEDIUM MPA (3µg/mL) TACROLIMUS (5µg/L) EVEROLIMUS (5µg/L) b/ Supplemental Digital Content 1 – Figure 1 b/ ns MEDIUM MPA (3µg/mL) TACROLIMUS (5µg/L) EVEROLIMUS (5µg/L)

Supplemental Digital Content 1 - Figure 1: Differential effects of MPA, tacrolimus and everolimus upon human CD4+ T cells in vitro polarization and IL17 production. a/ Effects of MPA, tacrolimus and everolimus upon the transcription of CD4+ cell subsets-related genes after two days of T cell activation. CD4+ T cells were activated following the same protocol, alone or in the presence of MPA and tacrolimus at a final concentration of 3µg/mL and 5µg/L, respectively. A comparative RT-PCR of the relative expression of CD4+ T cell subsets-related genes was then realized. *, P<0.05; **, P <0.01; ***, P <0.005 (Comparison of means, Wilcoxon signed-rank test, .Prism 5; Graph Pad Softwares, San Diego, Calif). Bars represent medians. b/ Effects of MPA, tacrolimus and everolimus upon IL17 secretion. CD4+ T cells from 18 healthy volunteers were activated for 48 hours alone or in the presence of MPA and tacrolimus at a final concentration of 3µg/mL and 5µg/L. Frequency of IL17-producing CD4+ T cells among 50 000 activated CD4+ T cells was measured by ELISpot. The figure presents the comparison of the frequency of IL17A.