This study was supported by the National Science Council of Taiwan through Grant NSC99-2314-B-038-002-MY3.
Virally inactivated human platelet concentrate lysate induces regulatory T cells and immunosuppressive effect in a murine asthma model
Version of Record online: 11 JAN 2013
© 2013 American Association of Blood Banks
Volume 53, Issue 9, pages 1918–1928, September 2013
How to Cite
Lee, Y.-L., Lee, L.-W., Su, C.-Y., Hsiao, G., Yang, Y.-Y., Leu, S.-J., Shieh, Y.-H. and Burnouf, T. (2013), Virally inactivated human platelet concentrate lysate induces regulatory T cells and immunosuppressive effect in a murine asthma model. Transfusion, 53: 1918–1928. doi: 10.1111/trf.12068
- Issue online: 9 SEP 2013
- Version of Record online: 11 JAN 2013
- Manuscript Accepted: 12 NOV 2012
- Manuscript Revised: 7 NOV 2012
- Manuscript Received: 3 OCT 2012
- National Science Council of Taiwan. Grant Number: NSC99-2314-B-038-002-MY3
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 CD4+ T cells were used to investigate the effects of PCL on expression of transcription factor forkhead box P3 (Foxp3), the inhibition of T-cell proliferation, and cytokine production. The regulatory function of PCL-converted CD4+ T cells was analyzed by suppressive assay. The BALB/c mice were given PCL-converted CD4+ 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.
PCL significantly enhanced the development of CD4+Foxp3+-induced regulatory T cells (iTregs). Converted iTregs produced neither Th1 nor Th2 cytokines and inhibited normal T-cell proliferation. PCL- and rHuTGF-β-converted CD4+ 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 Th2 responses in mice.
S/D-treated PCL promotes Foxp3+ iTregs and exerts immunosuppressive and anti-inflammatory properties. This finding may help to understand the clinical properties of platelet lysates.