Regulatory T Cells and Allergy Hanne Jarmer (CBS).
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Transcript of Regulatory T Cells and Allergy Hanne Jarmer (CBS).
Regulatory T Cells and Allergy
Hanne Jarmer (CBS)
Type I Hypersensitivity
A normal reaction against parasitesTypical allergens:
- pollen- penicillin- nuts- milk- bee venom- mold spores
Early Last Century
“Hmm..., maybe we can make a vaccine?”
Portuguese Man of War
Poul Portier and Charles Richet observed:
Early last century
Early Last Century
1. time: No reaction
2. time: Got sick died
Immediate Hypersensitivity
anaphylaxis
Richet got the Nobel Prize
The Mechanism
The Regulation
- presentation (concentration/mode)
- TH1, TH2 and TReg
Several factors are important:
- genetics
The Regulation
The Naive T cell will differentiate into different subsets induced by different cytokines
Naive T cell
Cytokines
TH1 TH2 TReg
TC
The Regulation
NaiveT cell
TH1 TH2 TReg
IL-12
IL-4IL-10 ?
CD4+ T cells - The normal state
TH1 TH2
TReg
- Keeping the balance
The allergic state
TH1
TH2
TReg
- Out of balance
Three types of TReg cells
IL-10 TGF-
CD25
CD25 = IL-2 receptor (IL2RA)
TReg1 TReg2 TReg3
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 inImmuno 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
normal allergicnormalCD4+CD25+
normalCD4+
allergic CD4+CD25+
allergicCD4+
Blood from 5 normal and 5 allergic patients
20 microarrays
The Microarray Experiments
20 microarrays
2-way ANOVA
NormalCD4+CD25+
NormalCD4+
Allergic CD4+CD25+
AllergicCD4+
2
2
1 1
2-way ANOVA
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-selfby Shimon Sakaguch
Natural Treg cells
Maybe ...
TReg
X
(TCR MHC-II)APC
Allergic TReg: Less XFewer active TReg cellsNo tolerance
CTLA-4 B7
Kristine Dahlin and Thomas Jensen
Thanks to
ALK-abello
Liu Anting, PhD from ALK