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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
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
The Naive T cell will differentiate into different subsets
induced by different cytokines
Naive T cell
Cytokines
TC
TH1
TH2
TReg
The Regulation
Naive
T cell
IL-12
IL-10 ?
IL-4
TH1
TH2
TReg
CD4+ T cells - The normal state
- Keeping the balance
TH1
TReg
TH2
The allergic state
- Out of balance
TReg
TH1
TH2
Three types of TReg cells
CD25
TReg1
TReg2
IL-10
TGF-
TReg3
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
normal
allergic
CD4+CD25+
CD4+CD25+
normal
allergic
CD4+
CD4+
20 microarrays
allergic
The Microarray Experiments
20 microarrays
2-way ANOVA
2
Normal
Allergic
CD4+CD25+
CD4+CD25+
1
1
Normal
Allergic
CD4+
CD4+
2
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
Maybe ...
CTLA-4
TReg
X
(TCR
B7
APC
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
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