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

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

Early last century

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

The Mechanism

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

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

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

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

The allergic state - Out of balance TReg TH1 TH2

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

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

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

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

The Microarray Experiments 20 microarrays

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

2-way ANOVA

The Regulatory T cell signal Natural Treg cells 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

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

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