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Regulatory T Cells and Allergy

Regulatory T Cells and Allergy. Hanne Jarmer (CBS). Type I Hypersensitivity. A normal reaction against parasites. Typical allergens: - pollen - penicillin - nuts - milk - bee venom - mold spores. Portuguese Man of War. Early Last Century.

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Regulatory T Cells and Allergy

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

  4. Early last century

  5. Early Last Century 2. time: Got sick  died 1. time: No reaction 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. Naive T cell Cytokines TC TH1 TH2 TReg The Regulation The Naive T cell will differentiate into different subsets induced by different cytokines

  9. IL-12 IL-10 ? IL-4 The Regulation Naive T cell 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. CD25 TReg2 TReg1 TReg3 IL-10 TGF- Three types of TReg cells CD25 = IL-2 receptor  (IL2RA)

  13. CD25+ TReg cells • Low proliferative capacity • Immunoregulatory properties • Induction of tolerance (?) • Antigen specific, cell-cell adhesion Potential use in Immuno Specific Therapy (SIT) ... or the other way around - in vaccines

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

  16. The Microarray Experiments 20 microarrays

  17. The Microarray Experiments

  18. The Microarray Experiments 20 microarrays

  19. 2 1 2 1 2-way ANOVA Normal CD4+CD25+ Allergic CD4+CD25+ Allergic CD4+ Normal CD4+

  20. 2-way ANOVA

  21. Allergy-Factor Results:

  22. Interaction Results:

  23. CD25 +/- effect (>250):

  24. Cell-cell adhesion CD80 (on immature DCs) CD152 CD2 T-cell act CD58 TReg MHC-II) (TCR C8/C9 CD59 SH2D1A/PTPN11 CDw150

  25. Interesting findings...

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

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