T Cells in Inflammatory Diseases - University of Birmingham · T Cells in Inflammatory Diseases...
Transcript of T Cells in Inflammatory Diseases - University of Birmingham · T Cells in Inflammatory Diseases...
T Cells in Inflammatory Diseases
Dagmar Scheel-Toellner
Rheumatology Research Group, IBRUniversity of Birmingham
T cell differentiationT cell precursor
Naïve T cell
Effector T cell Memory T cells
Effector function
Thymus
Sec. lymph. Tissue
APC in periphery
α/β, γ/δ α/β, γ/δ α/β, γ/δ α/β, γ/δ CD4 / CD8
EM / CMTh0 / Th1 / Th2 / Treg
Effector Functions of T Cells:
Help other immune cells CytokinesStimulatory Surface Proteins
Suppression / Regulation
Cytotoxicity
T cell help 1:Cytokines
Th1 Th2 ?
IFN-γγγγ, IL-2, LT IL-4, IL-5, IL-10 IL-3, TNF-αααα, TGF-ββββ, GM-CSF
Effector Functions of T Cells:
Help other immune cells Cytokines
Stimulatory Surface Proteins
Suppression / Regulation
Cytotoxicity
Effector Functions of T Cells:
Help other immune cells Cytokines
Stimulatory Surface Proteins
Suppression / Regulation
Cytotoxicity
T cells in SLE
B T
CD40 CD40L
Cytokines
B cell - anti DNA
T cell - anti histone
Hapten-Carrier response
Effector Functions of T Cells:
Help other immune cells Cytokines
Stimulatory Surface Proteins
Suppression / Regulation
Cytotoxicity
Effector Functions of T Cells:
Help other immune cells Cytokines
Stimulatory Surface Proteins
Suppression / Regulation
Cytotoxicity
Effector Functions of T Cells:Help other immune cells
Cytokines
Stimulatory Surface Proteins
Suppression / Regulation
Cytotoxicity
??
T cells in RA
Low rate of proliferation
Low response to stimulation
Very low level of cytokine production ex vivo
However:
T cells in RA
MHC association
T cell targeted therapies are beneficial
total lymph node irradiation
thoracic duct drainage
anti-CD4 therapy
Glucocorticoid injection
T cells in RA
Antigen specific?
Similar clonal expansions as in periphery.
Flu specific T cells in joint after vaccination.
T cells in RA
T
B
T
T
T T
T
T
T
T
T
T
T
B
B
BB
BB
T
B
TT T
T
T
T
T
T
T
T
B
B
BB
BB
CollagenaseRemove T cells
TNF-αααα
No TNF-αααα
T cells in RA
May be stimulated by an antigen independent mechanism
Help maintain the chronic inflammation by supporting TNF-αααα production.