Daan Pieren

77 Compromised DNA repair promotes the accumulation of regulatory T cells Proportion (%) CD25 + (%) PD-1 + (%) Naive Tregs Memory Tregs E F G H I J 0 5 10 15 20 %CD4 + FoxP3 + of CD3 + ** * ns Total Tregs Ercc1 +/+ Ercc1 -/ ∆ 7 Ercc1 -/ ∆ 7 + Rapamycin CD3 + T cells Memory CD4 + T cells Memory CD4 - T cells B C D A 0 20 40 60 % CD3 + of viable lymphocytes ** * ns 0 10 20 30 % CD44 Hi of CD4 + CD3 + cells ** ns * 0 10 20 30 % CD44 Hi of CD4 - CD3 + cells ** ** ns 0 5 10 15 20 25 % Treg of naive CD4 + *** 0.06 ns 70 80 90 100 % CD25 + of naive Treg ** 0.06 ns 0 10 20 30 40 % PD-1 + of naive Treg ** ns * 0 20 40 60 % Treg of memory CD4 + *** *** ns 40 60 80 100 % CD25 + of memory Treg *** *** ns 30 40 50 60 70 80 % PD-1 + of memory Treg *** *** ns Figure 4. eRapa increases the proportion of Tregs within the memory CD4 + T-cell subset. The frequencies of ( A ) total T cells (CD3 + cells of viable lymphocytes), ( B ) memory CD4 + T cells (CD44 Hi of CD4 + CD3 + cells), ( C ) memory CD4 - T cells (CD44 Hi of CD4 - CD3 + cells), and ( D ) total Tregs (CD4 + FoxP3 + of CD3 + ) were determined in the spleens of Ercc1 +/+ (n=6, blue bars), Ercc1 -/ Δ 7 (n=7, orange bars), and Ercc1 -/ Δ 7 treated with eRapa (n=6, grey bars). The frequencies of ( E ) naive Tregs (FoxP3 + cells of CD44 Lo CD4 + CD3 + ), and ( h ) memory Tregs (FoxP3 + cells of CD44 Hi CD4 + CD3 + ), and their respective ( F,I ) CD25 + and ( G,J ) PD-1 + cell frequencies were also determined in these mice. Bar graphs show mean ± SD; * p < 0.05, ** p < 0.01, *** p <0.001, ns = not statistically significant for the difference between groups using one-way ANOVA corrected with Holm-Sidak test for multiple comparisons. 3