Lin Lin

China Medical University (PRC), Feng-t’ien, Liaoning, China

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Publications (5)9.34 Total impact

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    ABSTRACT: Although the immunomodulative properties of mesenchymal stem cells (MSCs) open up attractive possibilities in solid-organ transplantation, information concerning the optimal dose, route, timing of administration, major histocompatibility complex (MHC)-restriction and relevant mechanisms is currently lacking. Therefore, better characterization of MSC immunoregulatory activity and elucidation of its mechanisms are crucial. In this study, we confirmed that MSCs did not elicit proliferation by allogeneic CD4(+) T cells, suggesting that MSCs were not immunogenic. By using C57BL/6 mouse MSCs as donor-derived or recipient-derived or as third-party MSCs, we discovered that MSCs suppressed CD4(+) T cell proliferation and prolonged mouse cardiac allograft survival in a dose-dependent and non-MHC-restricted manner. We also found that intraperitoneal administration favored survival prolongation, although this prolongation was weaker than that via the intravenous route. Only infusion at earlier time points favored survival prolongation. Depletion of CD4(+)CD25(+) T cells did not affect the immunosuppression of MSCs on CD4(+) T cells. Moreover, MSCs did not induce regulatory T cells. The in vivo data revealed that MSCs did not increase the percentage of CD4(+)CD25(+) T cells and FoxP3 expression. More importantly, we demonstrated for the first time that depletion of CD4(+)CD25(+) T cells did not hinder MSC-induced survival prolongation, indicating that CD4(+)CD25(+) regulatory T cells were not essential for the prolongation of MSC-mediated allograft survival.
    Cell and Tissue Research 08/2014; 358(2). DOI:10.1007/s00441-014-1956-z · 3.57 Impact Factor
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    ABSTRACT: Because of the anergy of CD25+CD4+ regulatory T cells, it is unclear how the number of these regulatory T cells is sustained and expanded in normal physiologic circumstances. In the present study, we examined the effect of natural allogeneic mature dendritic cells (DCs) on the proliferation and function of CD25+CD4+ T cells. Our data showed that natural allogeneic mature DCs stimulated CD25+CD4+ T-cell growth vigorously, whereas immature DCs had little effect on the proliferation of CD25+CD4+ T cells. After expansion by mature DCs, CD25+CD4+ T cells maintained their expression of Foxp3 and suppressed the proliferation of CD25- CD4+ T cells similar to freshly isolated CD25+CD4+ T cells. Our results introduce a potentially critical role played by natural allogeneic mature DCs, which exist in normal physiologic circumstances, in controlling CD25+CD4+ regulatory T-cell expansion and function.
    International surgery 10/2010; 95(4):329-34. · 0.47 Impact Factor
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    ABSTRACT: IFN-γ was documented to be commonly associated with acute rejection. In the present study, we investigated the role of IFN-γ in the transplant long-surviving induced by blocking CD40-CD40 ligand (CD40-CD40L) costimulation and its mechanisms. IFN-γ expression in cardiac allografts and spleens from syngeneic and allogeneic recipients with or without anti-CD40L monoclonal antibody (MR-1) treatment was examined by real-time RT-PCR. The grafts survival time in Wild type (IFN-γ(+/+)) and IFN-γ deficient (IFN-γ(-/-)) recipients was investigated. Mixed lymphocyte reaction (MLR) of CD4(+) T cells and cytotoxic T lymphocyte (CTL) assay of CD8(+) T cells were also studied. FoxP3 expression in allografts and spleens from IFN-γ(+/+) or IFN-γ(-/-) recipients with MR-1 treatment was examined. Furthermore, FoxP3, IL-10 and CTLA-4 expressions and the suppressive capability of CD4(+)CD25(+) regulatory T cells were examined. Rejected allografts showed significantly higher IFN-γ expression than long-surviving allografts. Allograft survival was not prolonged in nonimmunosuppressed IFN-γ(-/-) mice. Administration of MR-1 induced long-term survival in 90.1% of IFN-γ(+/+) recipients (98±6.6 days) but failed to do so in IFN-γ(-/-) group (16.2±4.0 days). IFN-γ(-/-) recipients facilitated the proliferation and CTL generation of T cells. The allografts and spleens from IFN-γ(+/+) recipients contained higher FoxP3 expression than IFN-γ(-/-) recipients. Moreover, CD4(+)CD25(+) T cells from IFN-γ(+/+) recipients displayed a higher FoxP3 and IL-10 expression and suppressive capability. IFN-γ plays an important role in the long-surviving induced by blocking CD40-CD40L through inhibiting the function of activated T cells and increasing suppressive capability of CD4(+)CD25(+) regulatory T cells.
    Transplant Immunology 10/2010; 24(2):113-8. DOI:10.1016/j.trim.2010.10.005 · 1.46 Impact Factor
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    ABSTRACT: We have demonstrated previously that CD4(+)CD25(+) regulatory T cells (Treg) are important for spontaneous hepatic allograft tolerance. In this study, we examine the role of Treg in cardiac allograft acceptance induced by blockade of the CD40-CD40L pathway. A heterotopic heart transplant model of major histocompatibility complex-mismatched mice was performed. Expression of forkhead/winged helix transcription factor (FoxP3) and/or the number of CD4(+)CD25(+) T cells in allografts and spleens were examined. The effect of Treg from the recipient or the donor on the induction and maintenance of long-term allograft survival was determined. Histologic analyses were also performed. The effects of Treg on CD4(+) and CD8(+) T cells were assessed. The levels of FoxP3 and/or CD4(+)CD25(+) T cells increased in long-surviving allografts and spleens. Depletion of Treg in the recipients but not the donors before transplantation caused rejection. Histologic analyses of allografts with Treg depletion showed extensive leukocyte infiltration and tissue destruction. However, delayed depletion of Treg in long-surviving recipients did not shorten their survival. Treg depletion increased the function of CD4(+) and CD8(+) T cells. Treg in the recipient but not in the donor is essential for long-term survival induced by CD40-CD40L blockade by inhibiting the function of CD4(+) and CD8(+) T cells; however, Treg are not important for maintenance. Both allograft and spleen are critical for induction of successful long-term survival.
    Surgery 09/2010; 149(3):336-46. DOI:10.1016/j.surg.2010.08.012 · 3.38 Impact Factor
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    ABSTRACT: We aimed to investigate whether tolerogenic dendritic cells (DCs) were induced in the tolerant recipients with the blockade of CD40-CD40L costimulation. Mouse heterotopic heart transplantation was performed. DCs were sorted from rejected and tolerant recipients using magnetic-activated cell sorting. Their expression of CD40, CD80, and CD86 was examined using fluorescence-activated cell sorting. DCs were stimulated with lipopolysaccharide in vitro, and interleukin 10 (IL-10) and IL-12 levels in the supernatants were evaluated using enzyme-linked immunosorbent assay. By using mixed leukocyte reaction, we investigated the stimulatory capacities and tolerogenic capability of DCs. DCs from tolerant recipients expressed lower level of costimulatory molecules, including CD40, CD80, and CD86 and released higher levels of IL-10 and lower levels of IL-12. In addition, DCs from tolerant recipients were weak stimulators of the mixed leukocyte reaction and inhibited the proliferation of splenocytes. IL-10(high)IL-12(low) DCs with immature phenotype were induced in the tolerant recipients with the blockade of CD40-CD40L costimulation, and they obtained the tolerogenic function.
    International surgery 04/2010; 95(2):135-41. · 0.47 Impact Factor

Publication Stats

14 Citations
9.34 Total Impact Points


  • 2010
    • China Medical University (PRC)
      Feng-t’ien, Liaoning, China