A Low-Molecular-Weight Dialysable Leukocyte Extract Selectively Enhances Development of CD4(+)ROR gamma t(+) T Cells and IL-17 Production

作者：Zajicova A; Javorkova E; Trosan P; Chudickova M; Krulova M; Holan V^*

来源：Folia Biologica, 2014, 60(6): 253-260.

• cytokine production
• IL-17
• low-molecular weight leukocyte extract
• RORgt
• Th17 cells

A low-molecular-weight (under 10 kDa) dialysable leukocyte extract (called transfer factor, TF) has been shown to be a prospective substance to improve or modulate immune response in autoimmunity, inflammation, infectious diseases or cancers. However, the use of TF has been limited by the absence of any data on the mechanism of its action. Here we show that TF prepared from peripheral blood leukocytes of healthy human donors displays multiple regulatory effects on individual parameters of the immune system. TF decreases proliferation of T and B lymphocytes and partially alters the production of cytokines and nitric oxide by activated macrophages. TF also inhibits production of T helper 1 (Th1) cytokines interleukin 2 (IL-2) and interferon gamma, slightly stimulates production of Th2 cytokine IL-10 and considerably enhances the secretion of IL-17 by activated mouse spleen T cells. At the molecular level, TF enhances expression of genes for transcription factor ROR gamma t and for IL-17. The enhanced expression of the RORgt gene corresponds with an increase in the number of ROR gamma t(+)CD4(+) Th17 cells and with enhanced IL-17 production. In contrast, the expression of the Foxp3 gene and the proportion of CD4(+)CD25(+)Foxp3(+) regulatory T cells are not significantly changed in the presence of TF. These results suggest that the activation of pro-inflammatory Th17 cells, which have multiple immunoregulatory properties, could be the main mechanism of the immunomodulatory action of a low-molecular-weight leukocyte extract.

• 出版日期2014