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Activated T cells exhibit increased uptake of silicon phthalocyanine Pc 4 and increased susceptibility to Pc 4-photodynamic therapy-mediated cell death

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Abstract

Photodynamic therapy (PDT) is an emerging treatment for malignant and inflammatory dermal disorders. Photoirradiation of the silicon phthalocyanine (Pc) 4 photosensitizer with red light generates singlet oxygen and other reactive oxygen species to induce cell death. We previously reported that Pc 4-PDT elicited cell death in lymphoid-derived (Jurkat) and epithelial-derived (A431) cell lines in vitro, and furthermore that Jurkat cells were more sensitive than A431 cells to treatment. In this study, we examined the effectiveness of Pc 4-PDT on primary human CD3+ T cells in vitro. Fluorometric analyses of lysed T cells confirmed the dose-dependent uptake of Pc 4 in non-stimulated and stimulated T cells. Flow cytometric analyses measuring annexin V and propidium iodide (PI) demonstrated a dose-dependent increase of T cell apoptosis (6.6–59.9%) at Pc 4 doses ranging from 0–300 nM. Following T cell stimulation through the T cell receptor using a combination of anti-CD3 and anti-CD28 antibodies, activated T cells exhibited increased susceptibility to Pc 4-PDT-induced apoptosis (10.6–81.2%) as determined by Pc 4 fluorescence in each cell, in both non-stimulated and stimulated T cells, Pc 4 uptake increased with Pc 4 dose up to 300 nM as assessed by flow cytometry. The mean fluorescence intensity (MFI) of Pc 4 uptake measured in stimulated T cells was significantly increased over the uptake of resting T cells at each dose of Pc 4 tested (50, 100, 150 and 300 nM, p < 0.001 between 50 and 150 nM, n = 8). Treg uptake was diminished relative to other T cells. Cutaneous T cell lymphoma (CTCL) T cells appeared to take up somewhat more Pc 4 than normal resting T cells at 100 and 150 nm Pc 4. Confocal imaging revealed that Pc 4 localized in cytoplasmic organelles, with approximately half of the Pc 4 co-localized with mitochondria in T cells. Thus, Pc 4-PDT exerts an enhanced apoptotic effect on activated CD3+ T cells that may be exploited in targeting T cell-mediated skin diseases, such as cutaneous T cell lymphoma (CTCL) or psoriasis.

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Authors and Affiliations

  1. Department of Dermatology, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland OH, USA

    David C. Soler, Jennifer Ohtola, Hideaki Sugiyama, Myriam E. Rodriguez, Ling Han, Minh Lam, Elma D. Baron, Kevin D. Cooper & Thomas S. McCormick

  2. The Murdough Family Center for Psoriasis, Cleveland OH 44106, USA

    David C. Soler, Hideaki Sugiyama, Myriam E. Rodriguez, Kevin D. Cooper & Thomas S. McCormick

  3. Department of Dermatology, Seirei Yokohama General Hospital, Kanagawa, Japan

    Hideaki Sugiyama

  4. Department of Radiation Oncology, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland OH, USA

    Nancy L. Oleinick

  5. Cleveland Louis Stokes Medical Center (VAMC), Cleveland, OH, USA

    Elma D. Baron & Kevin D. Cooper

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  1. David C. Soler
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  2. Jennifer Ohtola
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Soler, D.C., Ohtola, J., Sugiyama, H. et al. Activated T cells exhibit increased uptake of silicon phthalocyanine Pc 4 and increased susceptibility to Pc 4-photodynamic therapy-mediated cell death. Photochem Photobiol Sci 15, 822–831 (2016). https://doi.org/10.1039/c6pp00058d

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