DendriticcellsinregulatingTH1andTH2Development

While T cells and B cells carry out the actions of antigen-specific immune responses, antigen-presenting cells called dendritic cells are required for this to happen. The name of dendritic cells is based on their shape, with activated dendritic cells displaying long processes on their surface. When immature dendritic cells found throughout the body internalize and present antigen, they express markers that stimulate the activation of lymphocytes, and migrate to lymphocyte rich tissues like the spleen and lymph nodes to initiate immune responses. In addition to stimulating responses against antigens, dendritic cells also produce tolerance to self antigens.Dendritic cells can be derived from either myeloid or lymphoid lineages. Monocyte derived lineages (pDC1) stimulate Th1 cell differentiation while plasmacytoid (lymphoid) dendritic cells (pDC2) induce Th2 cell differentiation. Factors that stimulate the maturation of monocytes derived dendritic cells include GM-CSF, and IL-4. IL-3 stimulates the differentiation of pDC2 cells into DC2 cells. A variety of factors are involved in antigen-recognition and processing by immature dendritic cells and in the maturation of these cells. The transition to mature dendritic cells down-regulates the factors involved in antigen internalization, and increases the expression of MHC, costimulatory molecules involved in lymphocyte activation, adhesion molecules, and specific cytokines and chemokines. Toll-like receptors on the surface of immature dendritic cells recognize microbial components to induce dendritic cell maturation (see “Toll-like receptor pathway”). In addition to stimulating B cell responses, dendritic cells are potent activators of T cells. IL-12 secretion by dendritic cells stimulates T cell responses, particularly differentiation of Th1 cells that produce interferon-gamma and other pro-inflammatory cytokines (See “Th1/Th2 Differentiation” pathway). While IL-4 generally stimulates Th2 differentiation, the stimulation of Th2 cell formation by DC2 cells does not appear to involve IL-4. The stimulation of Th1 and Th2 cell formation by dendritic cells appears to be balanced by counter-regulation of each pathway by the other. Interferon-gamma produced by Th1 cells blocks the further stimulation of Th1 differentiation by DC1 cells. The IL-4 produced by Th2 cells kills dendritic cell precursors that contribute to Th2 cell creation. Direct interactions between T cells and dendritic cells are enhanced through the expression of adhesion molecules and costimulatory receptors CD80 and CD86 expressed by mature dendritic cells activate T cells in concert with the recognition of antigen/MHC by the T cell receptor. The central role of dendritic cells as modulators of immune responses makes them an important focus of studies about autoimmune disease, transplant rejection, allergies, responses to infections, and other alterations of the immune response.

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