title: Enhanced skin allograft survival after photodynamic therapy. Association with lymphocyte inactivation and macrophage stimulation.
abstract: It has been found previously that peritoneal exposure to hematoporphyrin derivative (HpD) photodynamic therapy (PDT) can induce systemic immunosuppression of contact hypersensitivity. We have now found that HpD-PDT also significantly prolongs survival of murine skin allografts. Normal A/J mice transplanted with BALB/c skin rejected the grafts within 10 +/- 0.9 days. Recipient mice treated 24 hr previously with HpD-PDT rejected skin allografts at 16 +/- 1.2 days. HpD alone or irradiation alone had no effect on skin graft survival, nor did HpD-PDT administered shortly after grafting. Flow cytometric analyses showed a nearly complete depletion of peritoneal lymphocytes 3 days after HpD-PDT. Lymphocyte levels were normal in the spleen, an organ not directly targeted by the PDT treatment, but the cells were totally unresponsive to Con A and LPS mitogens. Conversely, peritoneal HpD-PDT caused a striking enhancement in macrophage function as measured by phagocytosis of antibody-coated sheep erythrocytes. Humoral immunity to hen egg-white lysozyme was not significantly changed by HpD-PDT. These results demonstrate that HpD-PDT causes systemic immunosuppression of cellular immunity which, in turn, allows prolonged survival of allografts. Humoral immunity appears to remain largely unaffected by HpD-PDT and macrophages become activated, suggesting that this therapy might be more effective in specifically targeting T cell-mediated immunity than current immunosuppressive treatments.
authors.affiliation: Department of Urology, Medical College of Ohio, Toledo 43699-0008.
authors.forename: B
authors.initials: B
authors.lastname: Qin
authors.forename: S H
authors.initials: SH
authors.lastname: Selman
authors.forename: K M
authors.initials: KM
authors.lastname: Payne
authors.forename: R W
authors.initials: RW
authors.lastname: Keck
authors.forename: D W
authors.initials: DW
authors.lastname: Metzger
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D005069:Evaluation Studies as Topic; D006085:Graft Survival / Q000187:drug effects*; D006414:Hematoporphyrin Photoradiation; D007165:Immunosuppression Therapy / Q000379:methods; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000187:drug effects; D016038:Skin Transplantation / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014184:Transplantation, Homologous