Role of cytokines in Th1 and Th2 differentiation of lymphocytes

Role of cytokines in Th1 and Th2 differentiation of lymphocytes. CD4+ T-helper lymphocytes are able to augment both cellular and humoral immune responses. During an immune response, cytokines as a component of the microenvironment present during T-cell priming can influence the developmental pathway taken by responding naïve CD4+ T cells. The Th1 developmental pathway is largely driven by IL-12 activation, producing high levels of IFNγ and TNFα upon antigen stimulation, and is responsible for regulating cell-mediated immunity. The Th1 cytokine IFNγ also polarizes macrophages (innate immune cells) towards the M1 phenotype. Th2 differentiation, in contrast, is largely driven by IL-4 and is characterized by IL-4, IL-5, IL-10, and IL-13 secretion, which are primarily involved in the coordination of humoral immunity, eosinophilic inflammation, and control of helminth infections. The Th2 cytokines IL-4 and IL-13, as well as CCL2 from monocytes, drives macrophages toward M2 polarization leading to high expression of IL-10 and IL1RA. The Th1 and Th2 pathways are regulated by a balance of positive and antagonistic feedback loops. IFNγ enhances further Th1 development and suppresses Th2 differentiation, while IL-4 and IL-10 supports Th2 differentiation and suppresses Th1 differentiation. In addition, CD4+ CD25+ Foxp3+ T-regulatory cells (Tregs), a subset of CD4+ T cells, mediate general immune suppression and can drive macrophages toward “M2-like” phenotypes, which are important for the prevention of autoimmunity, but can suppress anti-tumor immunity [, , , ]

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Pretreatment levels of circulating Th1 and Th2 cytokines, and their ratios, are associated with ER-negative and triple negative breast cancers. () Chi-Chen Hong, et al. Breast Cancer Res Treat. ;139(2):477-488. Figure: F1. Homo sapiens

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