Typical cytokines secreted by types of CD4 T cells Notable TFs RORgT FOXP3 (some T regs) STAT1, T-bet, STAT4 STAT6, GATA3 Th17 IL-6, IL-17, IL-22 TGF-b, IL-10, +/- IL-4 Reg. CD4 T cell IL-2, IFN-g, TNF-alpha, TNF-beta (a.k.a: LT-alpha) Th1 IL-4, IL-5, IL-6, IL-10, IL-13 Th2 1
Overview of Th0 differentiation High IL-6, IL-23, TGF-beta CD25 CD4 T cell Tr1 or Th3 TGF-beta Low IL-6, IL-23 Low IFN-g & IL-4 IL-10 Th0 High IFN-g or IL-4 Th1 Th2 High IFN-g, IL-12 High IL-4 2
3 Cross-talk among CD4 T cell subsets Macrophage (impaired activation of other CD4 T cell subsets) IL-10 (-) T reg. TGF-b (-) Th1 IFN-g (-) TGF-b (-) Th17 IFN-g (-) IL-4 (-) Th2 IL-10 (-) Dendritic cell (decr. IL-12, decr. Th1 activation) [(-) = suppresses] 3
4 CLASSICAL PATHWAY: Ig + C1 ---> Ig-C1 C1 esterase activity C4 ------------------------------> C4b + C4a C2 ------------------------------> C2b + C2a C4b + C2a ---> C4b2a C4b2a C3 ---------------------------------> C3b + C3a C4b2a + C3b ---> C4b2a3b ALTERNATE PATHWAY: C3 -------> C3b + C3a (spontaneous) C3b + B ---> C3bB D C3bB --------------------> C3bBb + Ba C3bBb + P ---> C3bBbP [Note: P = Properdin] C3bBbP C3 --------------------------------> C3b + C3a C3bBb + C3b ---> C3bBb3b (a.k.a.: C3b2Bb) SHARED COMPONENTS: C5 convertase C5 -----------------------------------------------> C5b + C5a C5b + C6 + C7 + C8 + C9 ==> MAC 4