regulatory t cells and allergy
DESCRIPTION
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. - PowerPoint PPT PresentationTRANSCRIPT
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Regulatory T Cells and Allergy
Hanne Jarmer (CBS)
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Type I Hypersensitivity
A normal reaction against parasitesTypical allergens:
- pollen- penicillin- nuts- milk- bee venom- mold spores
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Early Last Century
“Hmm..., maybe we can make a vaccine?”
Portuguese Man of War
Poul Portier and Charles Richet observed:
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Early last century
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Early Last Century
1. time: No reaction
2. time: Got sick died
Immediate Hypersensitivity
anaphylaxis
Richet got the Nobel Prize
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The Mechanism
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The Regulation
- presentation (concentration/mode)
- TH1, TH2 and TReg
Several factors are important:
- genetics
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The Regulation
The Naive T cell will differentiate into different subsets induced by different cytokines
Naive T cell
Cytokines
TH1 TH2 TReg
TC
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The Regulation
NaiveT cell
TH1 TH2 TReg
IL-12
IL-4IL-10 ?
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CD4+ T cells - The normal state
TH1 TH2
TReg
- Keeping the balance
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The allergic state
TH1
TH2
TReg
- Out of balance
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Three types of TReg cells
IL-10 TGF-
CD25
CD25 = IL-2 receptor (IL2RA)
TReg1 TReg2 TReg3
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CD25+ TReg cells
- Low proliferative capacity
- Immunoregulatory properties
- Induction of tolerance (?)
- Antigen specific, cell-cell adhesion
Potential use inImmuno Specific Therapy (SIT)
... or the other way around - in vaccines
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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
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The Microarray Experiments
normal allergicnormalCD4+CD25+
normalCD4+
allergic CD4+CD25+
allergicCD4+
Blood from 5 normal and 5 allergic patients
20 microarrays
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The Microarray Experiments
20 microarrays
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The Microarray Experiments
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The Microarray Experiments
20 microarrays
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2-way ANOVA
NormalCD4+CD25+
NormalCD4+
Allergic CD4+CD25+
AllergicCD4+
2
2
1 1
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2-way ANOVA
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Allergy-Factor Results:
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Interaction Results:
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CD25 +/- effect (>250):
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Cell-cell adhesion
CD58 CD2 T-cell act
TReg
CD80 (on immature DCs)CD152
CD59
(TCR MHC-II)
CDw150 SH2D1A/PTPN11
C8/C9
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Interesting findings...
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Kristine Dahlin and Thomas Jensen
Thanks to
ALK-abello
Liu Anting, PhD from ALK