Figure 3.
Figure 3. DC plasticity in response to different maturation stimuli directs Th polarization. DCs can direct the fate of naive CD4+ T cells, depending on the type of DC maturation stimulus. Following priming, CD4+ T cells may differentiate toward T-helper 1 (Th1) cells, which produce IFNγ and support CD8+ cytotoxic T lymphocyte (CTL) responses, or toward T-helper 2 (Th2) cells, which produce IL-4, IL-5, and IL-13, support humoral immunity, and down-regulate Th1 responses. The direction of Th polarization is determined by the secreted cytokine profile of the stimulating DCs, which in turn depends on the DC subtype, the anatomic location of the DCs, and the type of maturation stimulus.45,56 These factors control other characteristics of the T-cell response as well, such as tolerance induction57 or T-cell homing.58,59 Th1-polarizing stimuli such as LPS or flagellin direct a DC differentiation program that causes the DCs to secrete IL-12p70, which together with IFNγ potently induce CD4+ T cells to differentiate into IFNγ-secreting Th1 effector cells. This T-cell program is mediated largely by the transcription factors signal transducer and activator of transcription 4 (Stat4) and T-bet.60,61 Th1 polarization can also be induced in the absence of IL-12p70 by mechanisms that are not entirely known but may be due in part to IL-12–related cytokines such as IL-27. Other DC maturation stimuli such as cholera toxin or schistosome eggs can differentiate DCs that do not produce IL-12p70 and that, in the presence of IL-4, induce naive CD4+ T cells to differentiate into IL-4–secreting Th2 effector cells. It is not clear whether Th2 polarization is induced by specific DC cytokines or is rather a default program carried out in the absence of a Th1 polarization signal from the DCs. However, DC secretion of chemokines such as thymus and activation-regulated chemokine (TARC) and MDC can act to potentiate a Th2 response by preferentially attracting Th2 cells. The Th2 program in CD4+ T cells is dependent on transcription factors GATA-3 and c-Maf.60,61

DC plasticity in response to different maturation stimuli directs Th polarization. DCs can direct the fate of naive CD4+ T cells, depending on the type of DC maturation stimulus. Following priming, CD4+ T cells may differentiate toward T-helper 1 (Th1) cells, which produce IFNγ and support CD8+ cytotoxic T lymphocyte (CTL) responses, or toward T-helper 2 (Th2) cells, which produce IL-4, IL-5, and IL-13, support humoral immunity, and down-regulate Th1 responses. The direction of Th polarization is determined by the secreted cytokine profile of the stimulating DCs, which in turn depends on the DC subtype, the anatomic location of the DCs, and the type of maturation stimulus.45,56  These factors control other characteristics of the T-cell response as well, such as tolerance induction57  or T-cell homing.58,59  Th1-polarizing stimuli such as LPS or flagellin direct a DC differentiation program that causes the DCs to secrete IL-12p70, which together with IFNγ potently induce CD4+ T cells to differentiate into IFNγ-secreting Th1 effector cells. This T-cell program is mediated largely by the transcription factors signal transducer and activator of transcription 4 (Stat4) and T-bet.60,61  Th1 polarization can also be induced in the absence of IL-12p70 by mechanisms that are not entirely known but may be due in part to IL-12–related cytokines such as IL-27. Other DC maturation stimuli such as cholera toxin or schistosome eggs can differentiate DCs that do not produce IL-12p70 and that, in the presence of IL-4, induce naive CD4+ T cells to differentiate into IL-4–secreting Th2 effector cells. It is not clear whether Th2 polarization is induced by specific DC cytokines or is rather a default program carried out in the absence of a Th1 polarization signal from the DCs. However, DC secretion of chemokines such as thymus and activation-regulated chemokine (TARC) and MDC can act to potentiate a Th2 response by preferentially attracting Th2 cells. The Th2 program in CD4+ T cells is dependent on transcription factors GATA-3 and c-Maf.60,61 

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