Blood Journal
Leading the way in experimental and clinical research in hematology

ICOS-LICOS interaction is critically involved in TGN1412-mediated T cell activation

  1. Sabrina Weissmüller1,
  2. Linda Y. Semmler2,
  3. Ulrich Kalinke2,
  4. Stefan Christians3,
  5. Jan Müller-Berghaus3, and
  6. Zoe Waibler1,*
  1. 1 Junior Research Group "Novel Vaccination Strategies and Early Immune Responses", Paul-Ehrlich-Institut, Langen, Germany;
  2. 2 Institute of Experimental Infection Research, TWINCORE, Centre of Experimental and Clinical Infection Research - a joint venture between MHH and HZI, Hannover, Germany;
  3. 3 Division of Immunology, Paul-Ehrlich-Institut, Langen, Germany
  1. * Corresponding author; email: zoe.waibler{at}


TGN1412, a superagonistic CD28-specific antibody, was shown to require Fc-crosslinking or immobilization as a prerequisite to mediate T cell proliferation and cytokine release in vitro. We used primary human umbilical vein endothelial cells (HUVECs) to study their ability to induce activation of TGN1412-treated T cells. We confirmed that peripheral primary human T cells do not show activation upon stimulation with soluble TGN1412 alone. Nevertheless, co-cultivation of TGN1412-treated T cells with HUVECs induced T cell activation that was further enhanced using cytokine pre-stimulated HUVECs. Unexpectedly, Fc-FcγR interaction was dispensable for endothelial cell-mediated proliferation of TGN1412-treated T cell. Transwell-culture assays showed that TGN1412-treated T cells need direct cell to cell contact to HUVECs to induce proliferation. We found that co-stimulatory ICOS-LICOS interaction between T cells and endothelial cells is critically involved in TGN1412-mediated effects. Blocking LICOS reduced TGN1412-mediated T cell proliferation significantly, whereas recombinant LICOS fully conferred TGN1412-mediated T cell proliferation. Of note, cytokine stimulation enhanced LICOS expression on HUVECs and ICOS-LICOS interaction upregulated ICOS expression on TGN1412-treated T cells. Hence, we provide a model of positive feedback conferred by ICOS-LICOS interaction between TGN1412-treated T cells and endothelial cells.

  • Submitted December 23, 2011.
  • Accepted April 25, 2012.