Transforming Growth Factor-beta (TGF-β) is a pleiotropic cytokine which exists in five isoforms, known as TGF-β1-5. TGF-β1 is the most abundant form in lymphoid organs and is found almost ubiquitously while other isoforms are expressed in a more restricted distribution. The biologically active forms of all isoforms are disulfide-linked homodimers. The heat- and acid- stable monomeric subunits have a length of 112 amino acids. TGF-β1 is produced in very high levels by platelets. Other cellular sources of TGF-β1 include macrophages, lymphocytes, endothelial cells, chondrocytes, and leukemic cells. TGF-β1 secretion can be induced by steroids, retinoids, EGF, NGF, vitamin D3, and IL-1. Activities of TGF-β1 include inhibition of cell growth for inhibitor for normal and transformed epithelial cells, endothelial cells, fibroblasts, neurons, and lymphoid cells and other hematopoietic cell types. TGF-β1 inhibits the proliferation of T cells and NK cells and down-regulates the activities of activated macrophages. TGF-β1 blocks the anti-tumor activity of IL-2-bearing lymphokine-activated killer (LAK) cells. TGF-β1 has a critical role in the development of regulatory T cells. Dendritic cells exposed to tumors have been reported to secrete TGF-β1 and stimulate expansion of naturally-occurring T reg cells. Moreover, TGF-β1 has been shown to act as a costimulatory factor for expression of Foxp3, leading to the differentiation of CD4+CD25+ Treg cells from peripheral CD4+CD25- progeny. TGF-β-induced regulatory T cells have been termed Ti-Treg.
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