1. Regulatory T Cells and Allergy
Hanne Jarmer (CBS)

2. Type I Hypersensitivity
A normal reaction against parasites
Typical allergens:
- pollen
- penicillin
- nuts
- milk
- bee venom
- mold spores

3. Early Last Century Poul Portier and Charles Richet observed:
Portuguese Man of War
“Hmm..., maybe we can make a vaccine?”

4. Early last century

5. Immediate Hypersensitivity Richet got the Nobel Prize
Early Last Century
1. time: No reaction
2. time: Got sick  died
Immediate Hypersensitivity
anaphylaxis
Richet got the Nobel Prize

6. The Mechanism

7. The Regulation
Several factors are important:
- genetics
presentation (concentration/mode)
- TH1, TH2 and TReg

8. The Regulation TC TH1 TH2 TReg
The Naive T cell will differentiate into different subsets induced by different cytokines
Naive T cell
Cytokines
TH1 TH2 TReg TC

9. The Regulation
Naive
T cell
IL-12
IL-4
IL-10 ?
TH1
TReg
TH2

10. CD4+ T cells - The normal state
- Keeping the balance
TH1
TH2
TReg

11. The allergic state
- Out of balance
TReg
TH1
TH2

12. Three types of TReg cells
CD25
TReg1
TReg2
TReg3
IL-10
TGF-
CD25 = IL-2 receptor  (IL2RA)

13. CD25+ TReg cells Low proliferative capacity
Immunoregulatory properties
T cell homeostasis
Prevents autoimmunity
Antigen specific, cell-cell adhesion
Induction of tolerance ... but how?
Potential use in
Immuno Specific Therapy (SIT) - graft tolerance
... or the other way around ...
in vaccines or cancer treatment

14. Microarray Project
The goal: Investigate the mechanism
 find cure for allergy or an effective SIT
The plan: Find the responsible genes by the
use of carefully designed microarray experiments

15. The Microarray Experiments
Blood from 5 normal and 5 allergic patients
normal
allergic
normal
CD4+CD25+
CD4+
allergic
20 microarrays

16. The Microarray Experiments
20 microarrays

17. 1 2-way ANOVA 2 Normal Allergic Normal Allergic CD4+CD25+ CD4+CD25+

18. 2-way ANOVA

19. The Regulatory T cell signal
Natural Treg cells
Nature Immunology  6, (2005)
Naturally arising Foxp3-expressing CD25+CD4+ regulatory
T cells in immunological tolerance to self and non-self
by Shimon Sakaguch

20. Fewer active TReg cells No tolerance
Maybe ...
CTLA-4 B7 X
APC
TReg
(TCR
MHC-II)
Allergic TReg: Less X
Fewer active TReg cells
No tolerance

21. Thanks to Liu Anting, PhD from ALK ALK-abello
Kristine Dahlin and Thomas Jensen