Figure 2. CD39 contributes to the suppressive function of Tr1 cells.

(a) Proliferation of responder CD4⁺ T cells (Tresp) stimulated in the presence of WT or Entpd1^−/− Tr1 cells. The suppression of proliferation is shown relative to the control group. (b) IL-10:GFP⁺ Tr1 cells from WT or Entpd1^−/− mice were transfered i.v. 10 days after EAE induction. The course of EAE is shown as the mean EAE score ± SEM (n = 5 mice per group). Effect of Tr1 genotype on disease course P<0.05 by two-way ANOVA. (c) Frequency of CD4⁺ splenic IFN-γ⁺, IL-17⁺ 21 days after EAE induction. (d) Proliferation of WT or CD73-deficient Tresp stimulated in the presence of WT or Entpd1^−/− Tr1 cells. (e) Proliferation of WT or CD73-deficient Tresp stimulated in the presence of WT or Nt5e^−/− DCs and WT or Entpd1^−/− Tr1 cells. (f-h) WT or Nt5e^−/− mice were immunized with MOG_35–55 and draining lymph nodes and spleens were collected 7 d after immunization, cultured for 48 h with MOG. CD4⁺ cells were then transferred intravenously into Rag1-deficient mice. Recipient mice were immunized with MOG_35–55 and on day 10, Tr1 cells from WT or Entpd1^−/− mice were administered i.v. into recipient mice. (g) The course of EAE is shown as the mean EAE score ± SEM (n = 5 mice per group). (h) Frequency of CD4⁺ splenic IFN-γ⁺, IL-17⁺ 21 days after EAE induction. (i) Body weight of Rag1^−/− mice transferred with WT CD90.1⁺CD4⁺CD25^–CD45RB^hi T cells alone or in combination with WT or CD39-deficient CD90.2⁺IL-10:GFP⁺ Tr1 cells. (j) Colon length, pathological scores and flow cytometry analysis of CD90.1⁺ IL-17 and IFN-γ producing cells and of CD90.2⁺ CD4+ T and IL-10⁺ CD90.2⁺ cells isolated from the lamina propria (LP) 8 weeks after colitis induction. Data are the mean ± SEM (a-h) of three independent experiments. *P<0.05; **P < 0.01.