1. An Essential Role for Interleukin 10 in the Function of Regulatory T Cells That Inhibit Intestinal Inflammation Barrette Kathleen – Dreesen Erwin Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F

2. Background

3. Inflammatory bowel diseases -Crohn’s disease -Ulcerative colitis

4. Inflammatory bowel diseases -Crohn’s disease -Ulcerative colitis

5. Inflammatory bowel diseases -Crohn’s disease -Ulcerative colitis

6. Murine models CD45RB high CD4+ T-cells C o l i t i s

7. CD45RB low CD4+ T cells T reg CD45RB high CD4+ T cells T h 1 Immune- suppressive Immune- stimulative

8. Question?

9. The role of IL-10 in IBD? “Is there evidence that IL-10 plays an important role in mucosal immune regulation?” IL-10 knock-out mice  enterocolitis (Kühn et al. 1993) rIL-10 administration  no colitis in SCID mice restored with CD45RB high CD4+ T cells (Powrie et al. 1994) CD45RB high CD4+ T cells, isolated from transgenic mice that expressed IL-10 under the IL-2 promotor failed to transfer colitis, but rather were able to inhibit colitis induced by WT CD45RB high CD4+ T cells (Hagenbaugh et al. 1997)

10. Experimental evidence?

11. IL-10 -/- mice  T reg ? Treatment with anti-IL-10(R) mAb  colitis? Colitis  T 1 h cells secreting IFN-g and TNF-a in the lesions

12. IL-10 -/- mice  T reg ? Treatment with anti-IL-10(R) mAb  colitis? Colitis  T 1 h cells secreting IFN-g and TNF-a in the lesions

13. CD45RB high CD4+ T-cells C o l i t i s

15. RAG-2 -/- mice 10-12 wk WT CD45RB high CD4+ T-cells C o l i t i s

18. RAG-2 -/- mice 10-12 wk WT C o l i t i s W CD45RB high CD4+ T-cells CD45RB low CD4+ T-cells

20. C o l i t i s

21. RAG-2 -/- mice 10-12 wk C o l i t i s W CD45RB low CD4+ T-cells IL-10 -/- WT CD45RB high CD4+ T-cells

23. C o l i t i s

24. RAG-2 -/- mice 10-12 wk C o l i t i s W CD45RB low CD4+ T-cells IL-10 -/-