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International Immunology, Vol. 12, No. 4, 479-486, April 2000
© 2000 Japanese Society for Immunology

Inhibition of the CD8+ T cell-mediated cytotoxicity reaction by hypericin: potential for treatment of T cell-mediated diseases

Gad Lavie1,2, Daniel Meruelo2, Karin Aroyo1 and Mathilda Mandel1

1 Institute of Hematology and Blood Transfusion Center, Sheba Medical Center, Tel-Hashomer 52621, Israel
2 Department of Pathology, New York University Medical Center, New York, NY 10016, USA

Correspondence to: G. Lavie, Institute of Hematology, Blood Transfusion Center, Sheba Medical Center, Tel-Hashomer 52621, Israel

The cytotoxicity reaction of murine CD8 T lymphocytes has been found to be strongly inhibited by nanomolar concentrations of hypericin, a lipophilic dianthraquinone with photodynamic properties. Cytotoxic T lymphocyte (CTL)-induced target cell apoptosis, as well as exocytosis of cytolytic granules from these cells, were ablated by hypericin, administered at the onset of the reaction, without affecting CTL viability. The inhibition of cytolysis occurred without the light irradiation which is essential for photosensitization. The findings suggest that the action of hypericin targets the effector CTL; however, apoptosis induced in murine L-cells with recombinant tumor necrosis factor (TNF)-{alpha} was also prevented by hypericin. Since hypericin is a known inhibitor of protein kinase C, MAP kinase and at least one other tyrosine kinase, this inhibitory activity could play a role in the down-modulation of CTL-induced cytotoxicity. Furthermore, our studies show that the action of hypericin induces rapid dephosphorylation of phospholipids associated with low-density membranes in CTL, but not with membranes of the cytotoxic granules. The ability of hypericin to interfere with cytotoxicity may render it useful in the treatment of T cell-mediated diseases.

Keywords: apoptosis, cytotoxic T lymphocyte, cytotoxicity, hypericin, protein kinase C, tumor necrosis factor-{alpha}

Transmitting editor: L. Steinman


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