Demonstration of a direct inhibitory effect of cyclosporine on normal human T-cells with two novel models of T-cell activation as probes Academic Article Article uri icon


MeSH Major

  • Antineoplastic Combined Chemotherapy Protocols
  • Breast Neoplasms
  • Hemangioblasts
  • Hematopoietic Stem Cells
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2


  • Two novel models of activation of human peripheral blood quiescent T-cells (T-cells) were utilized herein as probes to analyze the mechanisms and to locate the site of action of cyclosporine (CsA) in the T-cell activation pathway. Highly purified T-cells were activated, independently of accessory cells, with either crosslinked anti-CD2 + anti-CD3 monoclonal antibodies (mAbs) or with sn-1,2-dioctanoylglycerol (DAG) and ionomycin. CsA inhibited the expression of 55-kDa interleukin-2 receptors (IL-2R) and T-cell proliferation in these accessory cell-independent models of T-cell activation. Recombinant IL-2, over a wide range of concentrations that included different binding affinities of cellular receptors for IL-2, did not completely reverse CsA-associated inhibition of IL-2R expression and/or proliferation. In additional experiments, designed to examine early activation related events, CsA did not interfere with the increase in intracellular free calcium concentration initiated with anti-CD2, anti-CD3, anti-CD2 + anti-CD3 mAbs or with ionomycin. DAG-induced and PKC-activation-dependent down-regulation of cell surface expression of CD3 antigens was similarly unaffected by CsA. Our findings unambiguously indicate that CsA has a direct inhibitory effect on T-cells. Moreover, CsA's cellular site of action is distal to calcium mobilization and PKC activation but proximal to IL-2R expression and IL-2-dependent DNA synthesis in normal human T-cells.

publication date

  • April 15, 1989



  • Academic Article


Digital Object Identifier (DOI)

  • 10.1016/0008-8749(89)90187-1

PubMed ID

  • 2522829

Additional Document Info

start page

  • 195

end page

  • 204


  • 120


  • 1