Thymosin-α1 modulates dendritic cell differentiation and functional maturation from human peripheral blood CD14+ monocytes

Although thymosins have been demonstrated to have immunomodulatory effects, it is still not clear whether they could affect dendritic cells (DCs), the most professional antigen-presenting cells. The objective of this study was to determine the effect and potential mechanisms of thymosin-alpha 1 (T alpha 1) on DC differentiation and functional maturation. Human peripheral blood CD14(+) monocytes were purified by using a magnetic separation column and cultured with GM-CSF and IL-4 to differentiate into immature DCs (iDCs). In the presence of T alpha 1, iDC surface markers CD40, CD80, MHC class I and class II molecules were significantly upregulated as measured by flow cytemotry analysis. However, T beta 4 or T beta 10 did not show these effects on iDCs. There was an approximately 30% reduction in antigen (FITC-conjugated dextran)-uptake by T alpha 1-treated iDCs as compared with non-T alpha 1-treated iDCs. In addition, T alpha 1-treated matured DCs (mDCs) showed an increased stimulation of allogeneic CD3(+) T-cell proliferation as measured by a mixed-lymphocyte reaction assay. T alpha 1-treated mDCs also increased the production of several Th1- and Th2-type cytokines as measured by a Bio-Plex cytokine assay. Furthermore, rapid activation of p38 MAPK and NF kappa B was seen in T alpha 1-treated iDCs as measured by a Bio-Plex phosphoprotein assay. Thus, T alpha 1 significantly enhances DC differentiation, activation, and functions from human peripheral blood CD14(+) monocytes possibly through a mechanism of the activation of p38 MAPK and NF kappa B pathways. This study provides a basis to further evaluate T alpha 1 as a possible adjuvant for a DC-directed vaccine or therapy. (c) 2007 Elsevier B.V. All rights reserved.