|
Cytokines Secreted During T Cell Development See also factors affecting Th1/Th2 development See also cytokines secreted during Th development T-helper lymphocytes secrete a panel of cytokines which determine their functional role in immune regulation. Th cells are known to be divided into at least 4 subsets based on their cytokine production profile. Most CD4+ T cells in the periphery are naive T cells which produce mainly IL-2 and small amounts of IL-3 and GM-CSF. Th0 cells, which are at an intermediate stage of CD4+ T cell development between naive and Th1/Th2 cells have the pattern of cytokine production of both Th1 and Th2 cells. Th1 cells are biased toward secretion of IL-2, IFN-y, lymphotoxin and tumor necrosis factor-β, promoting cell-mediated immunity to intracellular pathogens: Th2 cells are biased toward secretion of IL-4, IL-5, IL-6, IL-9, IL-10 and IL-13, which function in allergy and humoral immunity to parasites. Differentation towards either the Th1 or Th2 phenotype is thought to be a consequence of several cellular influences directing T cell differentiation. See Factor which influence Th1/Th2 development Th1 TH1 cell subset secretes IL-2, IFN-y, and TNF-α. These cytokines induce nitric oxide (NO) synthase in macrophages to increase their microbicidal activity, and IFN-γ causes murine B cells to switch their Ig isotype to IgG1 which promotes phagocytosis by activating the classical pathway of complement and binding to Fc receptors on macrophages. IL-2: TH1 cells produce IL-2 that promote the differentiation of fully cytotoxic Tc cells from CD8+ precursors. This makes the TH1 subgroup well adapted for viral infections and intracellular pathogens. IL-12: Il-12 like IL-2 is capable of potentaiting T and natural killer cell-mediated cytotoxic responses. But IL-12 is a much stronger stimulator of TH1 CD4+ T cells. These cells are involved in the maturation of CD8+ T cells. INFγ: A defining cytokine of the TH1 subset, IFN-y, activates macrophages to increase microbicidal activity, up-regulate the level of class II MHC and secrete cytokines like IL-12 which induces TH cells to differentiate into the TH1 subset. IFN-y secretion by TH1 cells also induces antibody class switching to IgG classes that support phagocytosis and fixation of complement. TNF-B and IFN-y are cytokines that mediate inflammation, and it is their secretion that accounts for the association of TH1 cells with inflammatory phenomena such as delayed hypersensitivity. The production of INF-y cytokines by TH1 cells also promotes the differentiation of fully cytotoxic Tc cells from CD8+ precursors. This same effect is observed with the production of IL-2. Along with Th2 cells, Th1 cells also secret IL-3, TNF-α, and GM-CSF. Th2 The TH2 subset can also be distinguished based on the cytokines it secretes. The TH2 subset secretes Il-4, IL-5, IL-6, IL-10 and IL-13., which collectively mediate the growth and ativation of mast cells and eosinophils, direct murine B cell Ig switching to IgE and IgG4 and inhibit macrophage activation. IL-4: The secretion of IL-4 and IL-5 by the TH2 subset induces production of IgE and supports easinophil mediated attack on helminth (roundworm) infections. IL-4 promotes a pattern of class switching that produces IgG that does not activate the complement pathway. IL-4 also increases the extent to which B cells switch from IgM to IgE. IL-5: IL-6: IL-10: IL-4 and IL-10 suppress the expansion of TH1 cells. IL-10 as with IL-4 is an immunosuppressive cytokine. Th2 cells produce IL-4, IL-5, IL6, IL-9, IL-10 and IL-13. Along with Th2 cells, Th1 cells also secret IL-3, TNF-α, and GM-CSF. |
