Selective depletion of a thymocyte subset in vitro with an immunomodulatory photosensitizer.
Conventional photodynamic therapy (PDT) utilizes light-absorbing compounds that have anti-cancer activity upon visible light irradiation. PDT has also been utilized for the treatment of certain immune conditions. To further understand the action of PDT upon immune cells, DBA/2 mouse thymocytes were treated with the photosensitizer benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) and/or an apoptosis-inducing anti-Fas (APO-1, CD95) monoclonal antibody. Nanomolar levels of BPD-MA in combination with nonthermal visible light irradiation rapidly induced apoptosis as gauged by DNA fragmentation assays. Thymocytes were modestly more sensitive to PDT-induced apoptosis than mature splenic T cells. BPD-MA and light or the anti-Fas antibody decreased CD4(+)CD8(+) cell numbers while relatively sparing CD4(-)CD8(-), CD4(+)CD8(-), and CD4(-)CD8(+) thymocytes. In combination, anti-Fas antibody and PDT augmented activity levels of the apoptosis-related protease caspase-3, cleavage of the caspase-3 substrate poly(ADP) polymerase, and the proportion of cells exhibiting DNA fragmentation and further impacted CD4(+)CD8(+) thymocyte survival. Although CD4(+)CD8(+) thymocytes had the greatest sensitivity to photodynamic depletion, BPD-MA was taken up by the other major thymocyte subsets with equal or greater avidity. Since CD4(+)CD8(+) thymocytes are selectively impacted by PDT and anti-Fas antibody can act in concert with PDT to further cytotoxicity, thymocytes may be useful for the identification of factors that govern immune cell susceptibility to this form of phototherapy.
Jiang
H
H
QLT PhotoTherapeutics, Inc., 520 West 6th Avenue, Vancouver, British Columbia, V5Z 4H5, Canada.
Granville
D J
DJ
McManus
B M
BM
Levy
J G
JG
Hunt
D W
DW
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D006224:Cricetinae; D053938:DNA Fragmentation; D008027:Light; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011166:Porphyrins / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology*; D019014:fas Receptor / Q000378:metabolism
D017319:Photosensitizing Agents; D011166:Porphyrins; D019014:fas Receptor; C504224:benzoporphyrin D; D011065:Poly(ADP-ribose) Polymerases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases