The Regulation <ul><li>presentation (concentration/mode) </li></ul>- T H 1, T H 2 and T Reg Several factors are important: - genetics
The Regulation The Naive T cell will differentiate into different subsets induced by different cytokines Naive T cell Cytokines T H 1 T H 2 T Reg T C
The Regulation Naive T cell T H 1 T H 2 T Reg IL-12 IL-4 IL-10 ?
CD4 + T cells - The normal state T H 1 T H 2 T Reg - Keeping the balance
The allergic state T H 1 T H 2 T Reg - Out of balance
Three types of T Reg cells CD25 = IL-2 receptor (IL2RA) IL-10 TGF- CD25 T Reg 1 T Reg 2 T Reg 3
CD25 + T Reg cells <ul><li>Low proliferative capacity </li></ul><ul><li>Immunoregulatory properties </li></ul><ul><li>T cell homeostasis </li></ul><ul><li>Prevents autoimmunity </li></ul><ul><li>Antigen specific, cell-cell adhesion </li></ul><ul><li>Induction of tolerance ... but how? </li></ul>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 20 microarrays normal allergic normal CD4 + CD25 + normal CD4 + allergic CD4 + CD25 + allergic CD4 +
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-self by Shimon Sakaguch Natural T reg cells
Maybe ... T Reg X (TCR MHC-II) APC Allergic T Reg : Less X Fewer active T Reg cells No tolerance CTLA-4 B7
Kristine Dahlin and Thomas Jensen Thanks to ALK-abello Liu Anting, PhD from ALK
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