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Virally inactivated human platelet concentrate lysate induces regulatory T cells and immunosuppressive effect in a murine asthma model
Author(s) -
Lee YuehLun,
Lee LinWen,
Su ChenYao,
Hsiao George,
Yang YiYuan,
Leu SyJye,
Shieh YingHua,
Burnouf Thierry
Publication year - 2013
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12068
Subject(s) - immunoglobulin e , ovalbumin , sensitization , cytokine , immunology , microbiology and biotechnology , chemistry , transforming growth factor , biology , antibody , immune system
Background Platelet concentrate lysates ( PCLs ) are increasingly used in regenerative medicine. We have developed a solvent/detergent ( S / D )‐treated PCL . The functional properties of this preparation should be unveiled. We hypothesized that, due to transforming growth factor‐β1 ( TGF ‐β1) content, PCLs may exert immunosuppressive and anti‐inflammatory functions. Study Design and Methods PCL was prepared by S / D treatment, oil extraction, and hydrophobic interaction chromatography. The content of TGF ‐β in PCL was determined by enzyme‐linked immunosorbent assay. Cultured CD 4+ T cells were used to investigate the effects of PCL on expression of transcription factor forkhead box P 3 ( F oxp3), the inhibition of T ‐cell proliferation, and cytokine production. The regulatory function of PCL ‐converted CD 4+ T cells was analyzed by suppressive assay. The BALB / c mice were given PCL ‐converted CD 4+ T cells before ovalbumin ( OVA ) sensitization and challenge using an asthma model. Inflammatory parameters, such as the level of immunoglobulin E ( IgE ), airway hyperresponsiveness (AHR), bronchial lavage fluid eosinophils, and cytokines were assayed. Recombinant human ( rHu ) TGF ‐β1 was used as control. Results PCL significantly enhanced the development of CD 4+ F oxp3+‐induced regulatory T cells (iTregs). Converted iTregs produced neither Th 1 nor Th 2 cytokines and inhibited normal T ‐cell proliferation. PCL ‐ and rHuTGF ‐β‐converted CD 4+ T cells prevented OVA ‐induced asthma. PCL ‐ and rHuTGF ‐β‐modified T cells both significantly reduced expression levels of OVA ‐specific IgE and significantly inhibited the development of AHR, airway eosinophilia, and Th 2 responses in mice. Conclusion S / D ‐treated PCL promotes F oxp3+ iTregs and exerts immunosuppressive and anti‐inflammatory properties. This finding may help to understand the clinical properties of platelet lysates.