ENHANCED SKIN ALLOGRAFT SURVIVAL AFTER PHOTODYNAMIC THERAPY - ASSOCIATION WITH LYMPHOCYTE INACTIVATION AND MACROPHAGE STIMULATION

It has been found previously that peritoneal exposure to hematoporphyr in derivative (HpD) photodynamic therapy (PDT) can induce systemic imm unosuppression of contact hypersensitivity. We have now found that HpD -PDT also significantly prolongs survival of murine skin allografts. N ormal A/J mice transplanted with BALB/c skin rejected the grafts withi n 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 al one had no effect on skin graft survival, nor did HpD-PDT administered shortly after grafting. Flow cytometric analyses showed a nearly comp lete depletion of peritoneal lymphocytes 3 days after HpD-PDT. Lymphoc yte levels were normal in the spleen, an organ not directly targeted b y the PDT treatment, but the cells were totally unresponsive to Con A and LPS mitogens. Conversely, peritoneal HpD-PDT caused a striking enh ancement in macrophage function as measured by phagocytosis of antibod y-coated sheep erythrocytes. Humoral immunity to hen egg-white lysozym e was not significantly changed by HpD-PDT. These results demonstrate that HPD-PDT causes systemic immunosuppression of cellular immunity wh ich, in turn, allows prolonged survival of allografts. Humoral immunit y appears to remain largely unaffected by HpD-PDT and macrophages beco me activated, suggesting that this therapy might be more effective in specifically targeting T cell-mediated immunity than current immunosup pressive treatments.