Soluble thrombospondin-1 suppresses T cell proliferation and enhances IL-10 secretion by antigen presenting cells stimulated with phytohemagglutinin

Immunol Invest. 2001 May;30(2):143-56. doi: 10.1081/imm-100104022.


Thrombospondin-1 (TSP-1) is different from other components of the extracellular matrix (ECM) regarding its production and distribution. TSP-1 is considered to be released in large quantity in inflammatory sites and exogenously added TSP-1 does not bind to preformed ECM but instead binds to cells. To define the physiological role of TSP-1 in the immune system, we studied the influence of TSP-1 on the in vitro culture of T cells and antigen-presenting cells (APCs) in the presence of phytohemagglutinin. By adding soluble TSP-1 to the culture, T cell proliferation was suppressed and anti-inflammatory cytokine IL-10 secretion by APCs was enhanced. The enhanced expression of IL-10 was also demonstrated at the mRNA level by RT-PCR using multiprimer kit for cytokines. The suppression of T cell proliferation and the enhancement of IL-10 secretion with soluble TSP-1 was inhibited byadding RGDS peptide or heparin. This result indicates that the effect of soluble TSP-1 may be caused by binding to its ligand(s) on T cells and/or APCs, resulting in transducing regulatory signals to the cells or disturbing appropriate interaction between T cells and APCs. We therefore propose that TSP-1 is an immunosuppressive modulator which may play a role in inflammatory sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / drug effects*
  • Antigen-Presenting Cells / metabolism
  • Cell Division
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism*
  • Mitogens / pharmacology
  • Phytohemagglutinins / pharmacology
  • Solubility
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Thrombospondin 1 / metabolism
  • Thrombospondin 1 / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • Mitogens
  • Phytohemagglutinins
  • Thrombospondin 1
  • Tumor Necrosis Factor-alpha
  • Interleukin-10