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Vaccination with photodynamic therapy‐treated macrophages induces highly suppressive T‐regulatory cells
Author(s) -
Akilov Oleg E.,
Wu Mei X.,
Jin Yongzhu,
Zhou Zhuoyan,
Geskin Larisa J.,
Falo Louis D.,
Hasan Tayyaba
Publication year - 2011
Publication title -
photodermatology, photoimmunology and photomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.736
H-Index - 60
eISSN - 1600-0781
pISSN - 0905-4383
DOI - 10.1111/j.1600-0781.2011.00578.x
Subject(s) - vaccination , photodynamic therapy , immunology , medicine , cancer research , virology , chemistry , organic chemistry
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 10 6 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.