Type 1 and Type 2 helper cells - University of Medicine and ...Presentation Transcript
T Cell Subsets Yufang Shi University Professor Department of Molecular Genetics, Microbiology and Immunology UMDNJ-Robert Wood Johnson Medical School [email_address]
Major Histocompatibility Complex Antigen and T Cells I I I II II K D L Gene encoding Involved antigen Processing I - A I - E Complement Cytokine Chromosome 17 H - 2 loci 95% CD8 T cells CD4 5% CD8 T cells CD1.1 Chromosome 1 CD1.2 NKT cells Ib CIITA I I I II II K D L Gene encoding Involved antigen Processing I - A I - E Complement Cytokine Chromosome 17 H - 2 loci CD1.1 Chromosome 1 CD1.2 Ib CIITA Chromosome 2 2m
T cell subsets in MHC deficient mice Autoimmune _ _ _ + +/- _
Scharenberg et al. Nat Rev Immunol. 2007 T Cell Activation
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, Reciprocal Cellular and Humoral Immune Responses
The Discovery of Th1 and Th2 J. Immunol. 1986 IL-4 IL-4 IL-4
Analysis of Th1 and Th2 Cells 10.2 5.1 CON IL - 4 IFN -
Cell Surface Markers on Th1, and Th2. 1. CD27 is negatively expressed on Th2 cells. 2. CD30 is preferentially expressed on Th2 cells. 3. IL-12Rb2 expressed on Th1 4. IFN-gRb expressed on Th2 5. CCR3 preferentially expressed on Th2.
Th1 and Th2 Cells Do not Represent All CD4 + Cells 10.2 5.1 CON IL - 4 IFN -
Th1 7 and Treg Deenick and Tangye, Immunology and Cell Biology, 2009
Th1 7 Differentiation
Steps in the generation of Th17 cells. 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. (Awasthi and Kuchroo, International Immunology, 2009)
Produced by Th17, require the presence IL23 produced
IL-17A–F (5 members)
IL-17A, prototype disulfide-linked homodimer
IL-17F, homodimer or hetrodimer with IL-17A.
Activation of IL-17R induces the production of cytokines such
as IL-1, IL-6 and TNF- and chermokines
Th1 7 and Diseases
Rheumatoid arthritis (CIA).
Multiple sclerosis (EAE)
Inflammatory bowel disease a
High T h 17 cells. IL-17 induce the production of IL-6, IL-8 and TNF-
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.
Bacterial: Mycobacteria and Pneumocystis carinii
Viral: HIV and others
Regulatory CD4 + T Cells (Treg) CD25=IL-2R
Regulatory CD4 + T Cells (Treg)
CD4 + CD25 + Foxp3 + Immunosuppressive
Anti-CD25 enhances immune response
(Awasthi and Kuchroo, International Immunology, 2009) Reciprocal generation of Treg and Th17 cells Activation of naive T cells in the presence of IL-23 did not induce the generation of Treg or Th17 cells. Supplementation of TGF-β in the culture induced the generation of Foxp3+ Treg cells while the addition of IL-6 not only inhibited the induction of TGF-β-induced Foxp3 but also concomitantly induced the generation of Th17 cells.
Th3: Produce TGF-b, but not IL-4 or IFN-g. CD8 + T cells: Cytotoxic Can also be differentiated into Tc1, Tc2…,. CD8 + Foxp3 + cells have not been characterized CD8 + T cells are also immunosuppressive Other T cell Subsets