Thymosin-alpha1 modulates dendritic cell differentiation and functional maturation from human peripheral blood CD14+ monocytes

Immunol Lett. 2007 Jun 15;110(2):110-20. doi: 10.1016/j.imlet.2007.04.007. Epub 2007 May 15.


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-alpha1 (Talpha1) 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 Talpha1, iDC surface markers CD40, CD80, MHC class I and class II molecules were significantly upregulated as measured by flow cytemotry analysis. However, Tbeta4 or Tbeta10 did not show these effects on iDCs. There was an approximately 30% reduction in antigen (FITC-conjugated dextran)-uptake by Talpha1-treated iDCs as compared with non-Talpha1-treated iDCs. In addition, Talpha1-treated matured DCs (mDCs) showed an increased stimulation of allogeneic CD3(+) T-cell proliferation as measured by a mixed-lymphocyte reaction assay. Talpha1-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 NFkappaB was seen in Talpha1-treated iDCs as measured by a Bio-Plex phosphoprotein assay. Thus, Talpha1 significantly enhances DC differentiation, activation, and functions from human peripheral blood CD14(+) monocytes possibly through a mechanism of the activation of p38 MAPK and NFkappaB pathways. This study provides a basis to further evaluate Talpha1 as a possible adjuvant for a DC-directed vaccine or therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic
  • Cell Differentiation
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Humans
  • Lipopolysaccharide Receptors* / blood
  • Lipopolysaccharide Receptors* / immunology
  • Lymphocyte Culture Test, Mixed
  • Monocytes / cytology
  • Monocytes / immunology*
  • Monocytes / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Thymalfasin
  • Thymosin / analogs & derivatives*
  • Thymosin / immunology
  • Thymosin / metabolism


  • Adjuvants, Immunologic
  • Cytokines
  • Lipopolysaccharide Receptors
  • thymosin beta(4)
  • Thymosin
  • thymosin beta(10)
  • Thymalfasin