Properties of cD4+ Th1 and Th2 subsets Costimulator Cytokines produced lL4.L5,l13 IL-3, GM-CSF Cytokine receptor IL-18R CCR4. CCR8 CXCR4 CXCR3, CCR5 ands for E- and Antibody isotypes IgE IgG1 activation Classical Alternative ellular and Molecular Immunology, Updated 6th Edition Copyright 2009 by Saunders, an imprint of Elsevier, Inc. All rights reserved
Properties of CD4+ Th1 and Th2 subsets
Differentiation of th1 Subset .g Stimulated by intracellular microbes that infect or activate macrophages or nK cells Listeria, mycobacteria and Leishmania Important cytokines for the Th1 differentiation L-12 IFN lL-18 type I IFNs(in human Important transcription factors(te)for the Th1 differentiation T-bet: master requlator STAT4 STAT1
Differentiation of Th1 Subset ❖ Stimulated by intracellular microbes that infect or activate macrophages or NK cells Listeria, mycobacteria and Leishmania ❖ Important cytokines for the Th1 differentiation ❖ Important transcription factors (TF) for the Th1 differentiation ▪ IL-12 ▪ IFN- ▪ IL-18 ▪ type I IFNs (in human) ▪ T-bet: master regulator ▪ STAT4 ▪ STAT1
The molecular basis of th1 differentiation The interplay of signals from the T cell receptor, the cytokines IFN-y and IL-12 and the tf t-bet stat1 and stat4 L-12 STAT-4 IFN→→STAT-1 Ag recognition by TCR T-b A positive amplification loop between T-bet and IFN-Y
The molecular basis of Th1 differentiation The interplay of signals from the T cell receptor, the cytokines IFN- and IL-12, and the TF T-bet, STAT1, and STAT4 IL-12 STAT-4 IFN- STAT-1 Ag recognition by TCR T-bet A positive amplification loop between T-bet and IFN-
Differentiation of th1 subsets From other Dendritic cell T cell cellular T cell activation (e.g. NK cells 命N Early T cell ITbe differentiation STAT1 Activated macrophages. dendritic Amplification IFN-YI L12 TH1 cells TH1 and TH2 subsets Abbas et al: Cellular and Molecular Immunology, Updated 6th Edition Copyright 2009 by Saunders, an imprint of Elsevier, Inc. All rights reserved
Differentiation of Th1 subsets
Differentiation of th2 Subset Stimulated by microbes and antigens that cause persistent or repeated T cell stimulation with little inflammation or macrophage activation Helminth and allergens Important cytokines for the Th1 differentiation L-4 Important tf for the th2 differentiation GATA-3: master regulator ■STAT6
Differentiation of Th2 Subset ❖ Important TF for the Th2 differentiation ❖ Stimulated by microbes and antigens that cause persistent or repeated T cell stimulation with little inflammation or macrophage activation Helminth and allergens ❖ Important cytokines for the Th1 differentiation ▪ IL-4 ▪ GATA-3: master regulator ▪ STAT6