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ALK07.ppt Presentation Transcript

  • 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 “ Hmm..., maybe we can make a vaccine?” Poul Portier and Charles Richet observed: Portuguese Man of War
  • 4. Early last century
  • 5. 1. time: No reaction Immediate Hypersensitivity anaphylaxis Richet got the Nobel Prize Early Last Century 2. time: Got sick  died
  • 6. The Mechanism
  • 7. The Regulation
    • presentation (concentration/mode)
    - T H 1, T H 2 and T Reg Several factors are important: - genetics
  • 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. The Regulation Naive T cell T H 1 T H 2 T Reg IL-12 IL-4 IL-10 ?
  • 10. CD4 + T cells - The normal state T H 1 T H 2 T Reg - Keeping the balance
  • 11. The allergic state T H 1 T H 2 T Reg - Out of balance
  • 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. CD25 + T Reg 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 20 microarrays normal allergic normal CD4 + CD25 + normal CD4 + allergic CD4 + CD25 + allergic CD4 +
  • 16. The Microarray Experiments 20 microarrays
  • 17. 2-way ANOVA Normal CD4 + CD25 + Normal CD4 + Allergic CD4 + CD25 + Allergic CD4 + 2 2 1 1
  • 18. 2-way ANOVA
  • 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. Maybe ... T Reg X (TCR MHC-II) APC Allergic T Reg : Less X Fewer active T Reg cells No tolerance CTLA-4 B7
  • 21. Kristine Dahlin and Thomas Jensen Thanks to ALK-abello Liu Anting, PhD from ALK