Mechanistic Insights Into Achievement of Cardiac Allograft Long-term Survival by Treatment With Immature Dendritic Cells and Sub-dose Sirolimus

Tao, Ran; Wang, Lianfu; Chen, Cheng Hsu; Wang, Shi Ho; DeMarco, Richard; Lotze, Michael T.; Thai, Ngoc; Fung, John J.; Lü, Lina; Shen, Qian

doi:10.1016/j.healun.2005.10.005

Cited by 4 publications

(3 citation statements)

References 34 publications

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“…(4) Induce Treg: eleven studies reported Treg can be generated by Tol-DCs to promote cardiac allograft survival. (5) Induce chimerism: chimerism between donors and recipients is an effective way to induce immune tolerance. One study reported that adoptive transfusion of Tol-DCs effectively formed chimerism between donors and recipients, which may be an effective mechanism of long-term graft survival induced by Tol-DCs.…”

Section: Tol-dcs Prolongs Graft Survivalmentioning

confidence: 99%

“…Tolerogenic DCs (Tol‐DCs) is a group of cells with imDC phenotype, being able to stably induce T cells hypo‐reactivity and immune tolerance (4, 5). Based on the principles of evidence‐based medicine, a systematic review on whether Tol‐DCs can induce immune tolerance to allogeneic heart transplantation was conducted, aiming to comprehensively evaluate the impacts of the adoptive transfusion of Tol‐DCs on graft survival and discuss the ways and mechanisms of Tol‐DCs induction, in order to provide new ideas for future study and advance the clinical application of Tol‐DCs to achieve long‐term graft survival.…”

Section: Introductionmentioning

confidence: 99%

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Adoptive transfusion of tolerance dendritic cells prolongs the survival of cardiac allograft: a systematic review of 44 basic studies in mice

Shan

et al. 2012

J Evidence Based Medicine

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For fully MHC mismatched allogeneic heart transplant recipients of inbred mouse, adoptive transfusion of Tol-DC, which can be gene-modified, drug-intervened, cytokine-induced, spleen-derived or liver-derived, can clearly prolong the survival of cardiac allograft or induce immune tolerance. Gene-modified and drug-induced Tol-DC can prolong graft survival most obviously. Having better reliability and stability than drug-induction, gene-modification is the best way to induce Tol-DCs at present. One-time intravenous infusion of 2 × 10(6) Tol-DC is a simple and feasible way to induce long-term graft survival. Multiple infusions will prolong it but increase the risk and cost. Adoptive transfusion of Tol-DC in conjunction with immunosuppressive agents may also prolong the graft survival time.

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Section: Tol-dcs Prolongs Graft Survivalmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adoptive transfusion of tolerance dendritic cells prolongs the survival of cardiac allograft: a systematic review of 44 basic studies in mice

Shan

et al. 2012

J Evidence Based Medicine

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“…27 Monti et al 28 found a dose-dependent reduction of IFNg in T cells after SRL-DC stimulation. Finally, Tao et al 29 described how SRL-DC are resistant to maturation influencing immune reactivity and tolerance induction through downregulation of T-cell alloreactivity.…”

Section: Pbmc Production Of Il-12 and Il-18mentioning

confidence: 99%

The effect of sirolimus- or cyclosporine-based immunosuppression effects on T-cell subsets in vivo

Libetta

Sepe

Zucchi

et al. 2007

Kidney International

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While sirolimus (SRL) is thought to be a non-nephrotoxic agent, cyclosporine A (CsA) toxicity is a serious problem in kidney transplantation. We compared the effects of the two drugs on T-helper (Th) subsets in kidney transplant patients. We examined 24 first cadaver kidney recipients equally randomized to receive SRL/mycophenolate mofetil (MMF)/methylprednisolone (MP), or cyclosporine with either MMF or MP. The Th1 and Th2 subsets in peripheral blood were separated based on their production of interferon-gamma (INFgamma) or interleukin (IL)-4/IL-5. The lymphocytes were stimulated with phytohemoagglutinin or with allogenic CD3-depeted and irradiated antigen-presenting cells. Furthermore, the conversion potential of Th0 to Th1 was determined by measuring IL-12 and IL-18 levels after lipopolysaccharide challenge. When peripheral blood lymphocytes taken from SRL-treated patients were stimulated by phytohemoagglutinin, there were significantly lower INFgamma-producing cells compared with the lymphocytes taken from patients treated with CsA. The number of IL-4/IL-5-producing cells did not differ among the patient groups. Release of IL-12 but not IL-18 from peripheral lymphocytes following treatment with lipopolysaccharide was significantly lower in the SRL-treated patients. These results show that compared with CsA, SRL caused a significant decrease in the Th1 lymphocyte subset associated with a significant reduction of IL-12 release.

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Dendritic Cell Sphingosine 1-Phosphate Receptor-3 Regulates Th1–Th2 Polarity in Kidney Ischemia–Reperfusion Injury

Bajwa

Huang

et al. 2012

The Journal of Immunology

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Dendritic cells (DCs) are central to innate and adaptive immunity of early kidney IRI and strategies to alter DC function may provide new therapeutic opportunities. Sphingosine 1-phosphate (S1P) modulates immunity through binding to its receptors (S1P1-5) and protection from kidney IRI occurs in S1P3-deficient mice. Through a series of experiments we determined that this protective effect was due in part to differences between S1P3-sufficient and deficient DCs. Mice lacking S1P3 on bone marrow cells were protected from IRI and S1P3-deficient DCs displayed an immature phenotype. WT but not S1P3-deficient DCs injected into mice depleted of DCs prior to kidney IR reconstituted injury. Adoptive transfer (i.e, i.v. injection) of glycolipid (antigen)-loaded WT but not S1P3-deficient DCs into WT mice exacerbated IRI, suggesting that WT but not S1P3-deficient DCs activated NKT cells. Whereas WT DC transfers activated the Th1-IFN-γ pathway, S1P3-deficient DCs activated the Th2-IL4 pathway and an IL4 blocking antibody reversed protection from IRI supporting the concept that IL-4 mediates the protective effect of S1P3-deficient DCs. Administration of S1P3-deficient DCs 7 days prior to or 3 h after IRI protected mice from IRI and suggests their potential use in cell-based therapy. We conclude that absence of DC S1P3 prevents DC maturation and promotes a Th2-IL4 response. These findings highlight the importance of DC S1P3 in modulating NKT cell function and IRI and support development of selective S1P3 antagonists for tolerizing DCs for cell based therapy or for systemic administration for the prevention and treatment of IRI and autoimmune diseases.

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Mechanistic Insights Into Achievement of Cardiac Allograft Long-term Survival by Treatment With Immature Dendritic Cells and Sub-dose Sirolimus

Cited by 4 publications

References 34 publications

Adoptive transfusion of tolerance dendritic cells prolongs the survival of cardiac allograft: a systematic review of 44 basic studies in mice

Adoptive transfusion of tolerance dendritic cells prolongs the survival of cardiac allograft: a systematic review of 44 basic studies in mice

The effect of sirolimus- or cyclosporine-based immunosuppression effects on T-cell subsets in vivo

Dendritic Cell Sphingosine 1-Phosphate Receptor-3 Regulates Th1–Th2 Polarity in Kidney Ischemia–Reperfusion Injury

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