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T Cells in Inflammatory Diseases
Dagmar Scheel-Toellner
Rheumatology Research Group, IBRUniversity of Birmingham
Lecture contents:
T cell functions
T cells in inflammatory disease
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
T cell help 2:Expression of Stimulatory Surface Proteins
Regulatory T- cells
T cell cytotoxicity
T cell cytotoxicityCTL Target cell
GranyzmeB
TCR MHC I
CD 8
Fas L Fas
Perforin
T cells in inflammatory disease
What is inflammation?
Lawrence et al Nat Rev Immunol 2002
Effector Functions of T Cells:
Help other immune cells Cytokines
Stimulatory Surface Proteins
Suppression / Regulation
Cytotoxicity
T cells in GranulomatousInflammation: Leprosy
T cells in Granulomatous Inflammation
T cells in GranulomatousInflammation
T cells in Granulomatous Inflammation
Effector Functions of T Cells:
Help other immune cells Cytokines
Stimulatory Surface Proteins
Suppression / Regulation
Cytotoxicity
T cells in SLEPhotosensitive Autoantibodies Immune complexes
Skin
Kidney
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
Colitis
Treg in Colitis(In mice)
Effector Functions of T Cells:
Help other immune cells Cytokines
Stimulatory Surface Proteins
Suppression / Regulation
Cytotoxicity
Cytotoxic T cells in Type 1 Diabetes
Cytotoxic T cells in Type 1 Diabetes(In mice)
Effector Functions of T Cells:Help other immune cells
Cytokines
Stimulatory Surface Proteins
Suppression / Regulation
Cytotoxicity
??
Outside Inside Histology
Rheumatoid Arthritis
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
Alternative mechanism of activation
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IL-6, TNF-αααα, IL-2
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T cells in RA
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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.
Effector Functions of T Cells:
Help other immune cells
Suppression / Regulation
Cytotoxicity
The Chronic Inflammatory Infiltrate in Rheumatoid Joints
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T cell differentiation
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