Selective action of the photosensitizer QLT0074 on activated human T lymphocytes.
A new photosensitizer, presently designated QLT0074, may have the potential for the treatment of immune and nonimmune conditions with photodynamic therapy (PDT). The activity of QLT0074 was tested against human peripheral blood T cells and Jurkat T lymphoma cells. At low nanomolar concentrations of QLT0074 in combination with blue light, apoptosis was rapidly induced in Jurkat and blood T cells in vitro as indicated by the expression of the apoptosis-associated mitochondrial 7A6 marker and Annexin-V labeling. Further studies performed with Jurkat T cells showed that PDT-induced apoptosis with QLT0074 was associated with caspase-3 activation and the cleavage of the caspase substrate poly(adenosine diphosphate-ribose)polymerase. Flow cytometry studies revealed that blood T cells with high expression of the interleukin-2 receptor (CD25) took up greater amounts of QLT0074 and were eliminated to a greater extent with PDT than T cells with low levels of this activation marker. This selective action of PDT was confirmed by similar reductions in the percentage of T cells that expressed other activation-related markers, including very late activation antigen-4 (CD49d), human leukocyte antigen DR (HLA-DR), intercellular adhesion molecule-1 (CD54) and Fas (CD95). For activated T cells treated with a specific dose of QLT0074 and light 24 h earlier, CD25 expression density was significantly less, whereas CD54, CD95 and HLA-DR levels were similar to those for control cells treated with light alone. This work shows that PDT with QLT0074 exerts selective, dose-related effects on T cells in vitro.
Jiang
Huijun
H
QLT Inc., 887 Great Northern Way, Vancouver, British Columbia, Canada.
Granville
David J
DJ
North
John R
JR
Richter
Anna M
AM
Hunt
David W C
DW
D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008297:Male; D018462:Photobiology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects
D017319:Photosensitizing Agents