Regulatory T Cells and Allergy Hanne Jarmer (CBS)
Type I Hypersensitivity A normal reaction against parasites Typical allergens: - pollen - penicillin - nuts - milk - bee v...
Early Last Century “ Hmm..., maybe we can make a vaccine?” Poul Portier and Charles Richet observed: Portuguese Man of War
Early last century
1. time: No reaction Immediate Hypersensitivity anaphylaxis Richet got the  Nobel Prize Early Last Century 2. time: Got si...
The Mechanism
The Regulation <ul><li>presentation  (concentration/mode) </li></ul>- T H 1, T H 2 and T Reg Several factors are important...
The Regulation The Naive T cell will differentiate into different subsets induced by different cytokines Naive T cell Cyto...
The Regulation Naive T cell T H 1 T H 2 T Reg IL-12 IL-4 IL-10 ?
CD4 +  T cells - The normal state T H 1 T H 2 T Reg - Keeping the balance
The allergic state T H 1 T H 2 T Reg - Out of balance
Three types of T Reg  cells CD25  =  IL-2 receptor    (IL2RA) IL-10 TGF-  CD25 T Reg 1 T Reg 2 T Reg 3
CD25 +  T Reg  cells <ul><li>Low proliferative capacity  </li></ul><ul><li>Immunoregulatory properties </li></ul><ul><li>T...
Microarray Project The goal:   Investigate the mechanism    find cure for allergy or an effective SIT The plan:   Find th...
The Microarray Experiments Blood from 5 normal and 5 allergic patients 20 microarrays normal allergic normal CD4 + CD25 + ...
The Microarray Experiments 20 microarrays
2-way ANOVA Normal CD4 + CD25 + Normal CD4 + Allergic CD4 + CD25 + Allergic CD4 +   2 2 1 1
2-way ANOVA
The Regulatory T cell signal Nature Immunology    6 , 345 - 352 (2005) Naturally arising Foxp3-expressing CD25+CD4+ regula...
Maybe ...  T Reg X (TCR MHC-II) APC Allergic T Reg : Less X Fewer active T Reg  cells No tolerance CTLA-4 B7
Kristine Dahlin and Thomas Jensen Thanks to ALK-abello Liu Anting, PhD from ALK
Upcoming SlideShare
Loading in...5
×

ALK07.ppt

417

Published on

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total Views
417
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
13
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

ALK07.ppt

  1. 1. Regulatory T Cells and Allergy Hanne Jarmer (CBS)
  2. 2. Type I Hypersensitivity A normal reaction against parasites Typical allergens: - pollen - penicillin - nuts - milk - bee venom - mold spores
  3. 3. Early Last Century “ Hmm..., maybe we can make a vaccine?” Poul Portier and Charles Richet observed: Portuguese Man of War
  4. 4. Early last century
  5. 5. 1. time: No reaction Immediate Hypersensitivity anaphylaxis Richet got the Nobel Prize Early Last Century 2. time: Got sick  died
  6. 6. The Mechanism
  7. 7. The Regulation <ul><li>presentation (concentration/mode) </li></ul>- T H 1, T H 2 and T Reg Several factors are important: - genetics
  8. 8. The Regulation The Naive T cell will differentiate into different subsets induced by different cytokines Naive T cell Cytokines T H 1 T H 2 T Reg T C
  9. 9. The Regulation Naive T cell T H 1 T H 2 T Reg IL-12 IL-4 IL-10 ?
  10. 10. CD4 + T cells - The normal state T H 1 T H 2 T Reg - Keeping the balance
  11. 11. The allergic state T H 1 T H 2 T Reg - Out of balance
  12. 12. Three types of T Reg cells CD25 = IL-2 receptor  (IL2RA) IL-10 TGF-  CD25 T Reg 1 T Reg 2 T Reg 3
  13. 13. CD25 + T Reg cells <ul><li>Low proliferative capacity </li></ul><ul><li>Immunoregulatory properties </li></ul><ul><li>T cell homeostasis </li></ul><ul><li>Prevents autoimmunity </li></ul><ul><li>Antigen specific, cell-cell adhesion </li></ul><ul><li>Induction of tolerance ... but how? </li></ul>Potential use in Immuno Specific Therapy (SIT) - graft tolerance ... or the other way around ... in vaccines or cancer treatment
  14. 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. 15. The Microarray Experiments Blood from 5 normal and 5 allergic patients 20 microarrays normal allergic normal CD4 + CD25 + normal CD4 + allergic CD4 + CD25 + allergic CD4 +
  16. 16. The Microarray Experiments 20 microarrays
  17. 17. 2-way ANOVA Normal CD4 + CD25 + Normal CD4 + Allergic CD4 + CD25 + Allergic CD4 + 2 2 1 1
  18. 18. 2-way ANOVA
  19. 19. The Regulatory T cell signal Nature Immunology   6 , 345 - 352 (2005) Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self by Shimon Sakaguch Natural T reg cells
  20. 20. Maybe ... T Reg X (TCR MHC-II) APC Allergic T Reg : Less X Fewer active T Reg cells No tolerance CTLA-4 B7
  21. 21. Kristine Dahlin and Thomas Jensen Thanks to ALK-abello Liu Anting, PhD from ALK
  1. A particular slide catching your eye?

    Clipping is a handy way to collect important slides you want to go back to later.

×