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Keywords:

  • Leishmania;
  • macrophage;
  • tolerance;
  • T regulatory cells;
  • vaccination

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 (MΦ). Two weeks after the last vaccination, mice were infected intradermally with 106 promastigotes of Leishmania major.

Results: Mice that received PDT-induced apoptotic MΦ had fewer parasites and higher numbers of Treg than mice vaccinated with thaw-frozen necrotic MΦ 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 MΦ. The role of Treg in this process was confirmed through Treg transfer from vaccinated to naïve mice. Mice receiving CD4+CD25+ cells from mice vaccinated with PDT-induced apoptotic MΦ showed smaller lesions 3 weeks after infection and lower parasitic burdens than mice that received Tregs from mice of thaw-frozen necrotic MΦ or PBS groups. These changes were mediated by the depletion of CD3+CD8+ and NKT cells and increased levels of IL-12p70 and interferon-γ, IL-10, and TGF-β in the cutaneous leishmaniasis lesions.

Conclusion: Vaccination with apoptotic MΦ-induced tolerogenic Treg cells that limited collateral tissue damage and diminished parasitic burden.