BACKGROUND/PURPOSE: The present study explores whether photodynamic therapy (PDT)-induced apoptosis can increase the number of tolerogenic regulatory T cells (Treg) and limit collateral tissue damage.METHODS: BALB/c mice were vaccinated subcutaneously three times with PDT-induced apoptotic or thaw-frozen, necrotic non-infected autologous macrophages (MÖ). Two weeks after the last vaccination, mice were infected intradermally with 10(6) promastigotes of Leishmania major.RESULTS: Mice that received PDT-induced apoptotic MÖ had fewer parasites and higher numbers of Treg than mice vaccinated with thaw-frozen necrotic MÖ or phosphate-buffered saline (PBS). Interleukin (IL)-4 and IL-6 were significantly suppressed, while IL-10 was increased in mice that received the PDT-induced apoptotic MÖ. The role of Treg in this process was confirmed through Treg transfer from vaccinated to na?ve mice. Mice receiving CD4(+) CD25(+) cells from mice vaccinated with PDT-induced apoptotic MÖ showed smaller lesions 3 weeks after infection and lower parasitic burdens than mice that received Tregs from mice of thaw-frozen necrotic MÖ or PBS groups. These changes were mediated by the depletion of CD3(+) CD8(+) and NKT cells and increased levels of IL-12p70 and interferon-ã, IL-10, and TGF-â in the cutaneous leishmaniasis lesions.CONCLUSION: Vaccination with apoptotic MÖ-induced tolerogenic Treg cells that limited collateral tissue damage and diminished parasitic burden.
Animals Apoptosis