Beruflich Dokumente
Kultur Dokumente
Yufang Shi
University Professor
Department of Molecular Genetics, Microbiology and Immunology
UMDNJ-Robert Wood Johnson Medical School
shiyu@umdnj.edu
Major Histocompatibility Complex Antigen and T Cells
K
Involved antigen
Processing I-A I-E D L Ib
I II II I I
Chromosome 2 b2m
Chromosome 1
CD1.1 CD1.2
T cell subsets in MHC deficient mice
Kb-/-Db-/-CIITA-/- - + + - - +* +
b 2m-/- + - - + - - +/-
_
b2m-/- CIITA-/- - - - - - -
T Cell Activation
B7.1 CD28
CTLA4
Co-stimulatory
B7.2
CD40 CD40L pairs
ICOSL ICOS
Cytokine/Cytokine
Receptors
The Cytokine Network
T Cell Subsets
Reciprocal Cellular and Humoral Immune Responses
Rats injected with repeated doses of flagellin (Salmonella adelaide) varying in doses developed specific antibody
response (purple squares) and delayed-type hypersensitivity (DTH; red squares), Parish and Liew, 1972,
The Discovery of Th1 and Th2
J. Immunol. 1986
Differential Expression of Cytokines by Th1 and Th2 cells
TNF-a + +
MIP-1a + +
MIP-1b + +
TCA-3 + +
IL-4 - + + -
IL-5 - + + -
IL-6 - +
IL-9 - +
IL-10 - + -
In Vitro Generation of T Helper Subsets
Naïve T Cells
- CD3
- CD28
vv vv
IL-4
Th0
IL-12
Suicide FasL
Fas Th2
Th1 TRAIL
DR4 Anti-Inflammatory
Pro-Inflammatory
Cytokines Cytokines
IL-4
IFN-g
IL-10
IL-2
IL-13
LT
IL-5
Th1 response IL-6
Cellular Immunity Th2 response
DTH Humoral Immunity
Acute Hypersensitivity
Th1/Th2 and Diseases
• Autoimmune Diseases
• Infections
CON
5.1
IL-4
10.2
IFN-g
Cell Surface Markers on Th1, and Th2.
CON
5.1
IL-4
10.2
IFN-g
Th17 and Treg
The activation of naive T cells in the presence of TGF-β and IL-6 initiates the Th17 differentiation
pathway. Th17 cells produce IL-21, which further amplifies Th17 generation in an autocrine manner.
IL-21 also induces the IL-23R on differentiated Th17 cells to make them responsive to IL-23
signaling. IL-23 stabilizes the Th17 phenotype by secreting IL-17A, IL-17F and IL-22 and helping
Th17 cells to acquire effector functions. STAT-3 plays an important role in Th17 differentiation,
amplification and stabilization as IL-6, IL-21 and IL-23 signals through STAT-3.
• IL-17A–F (5 members)
• Autoimmune disease:
Rheumatoid arthritis (CIA).
Multiple sclerosis (EAE)
Inflammatory bowel disease a
Psoriasis
High Th17 cells. IL-17 induce the production of IL-6, IL-8 and TNF-
• Infections:
Important for both intracellular and extracellular pathogens.
IL-17 up-regulates specific chemokines, pro-inflammatory cytokines
and colony-stimulating factors (CSFs), thereby helping to induce
neutrophils and other myeloid cells recruitment at the site of infection.
CD25=IL-2Ra
Regulatory CD4+ T Cells (Treg)
• CD4+CD25+Foxp3+ Immunosuppressive
From Bubnoff
Reciprocal generation of Treg and Th17 cells