Developing Immunologic Tolerance for Transplantation at the Fetal Stage

Mendieta-Zerón, Hugo

doi:10.2217/imt.11.142

Cited by 4 publications

(3 citation statements)

References 95 publications

(69 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although non-specific immunosuppressants can suppress immune rejection and prolong allograft survival, long-term use of these drugs causes serious adverse reactions, such as increased occurrence of opportunistic infections or increased cancer recurrence rate [2]. Thus, donor specific tolerance must be established and maintained to reduce the dosage of immunosuppressants [3].…”

Section: Introductionmentioning

confidence: 99%

Tolerance Induction by Exosomes from Immature Dendritic Cells and Rapamycin in a Mouse Cardiac Allograft Model

Yang

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

BackgroundDendritic cells (DCs) release bioactive exosomes that play an important role in immune regulation. Because they express low levels of class I major histocompatibility complex (MHC) and co-stimulatory molecules, exosomes derived from donor immature DCs (imDex) prolong allograft survival by inhibiting T-cell activation. However, this effect is limited and does not induce immunological tolerance when imDex are administered alone. Thus, we tested the effect of combined treatment with donor imDex and low-dose rapamycin on inducing tolerance in a mouse cardiac transplantation model.MethodsImDex were obtained from the culture supernatant of immature DCs derived from donor mouse (C57BL/6) bone marrow and were injected with suboptimal doses of rapamycin into recipient mouse (BALB/c) before and after transplantation. The capacity of this treatment to induce immune tolerance was analyzed in vitro and in vivo using the mouse cardiac transplantation model.ResultsDonor imDex expressed moderate levels of MHC class II and low levels of MHC class I and co-stimulatory molecules, but neither imDex nor subtherapeutic rapamycin dose alone induced cardiac allograft tolerance. Combined treatment with imDex and rapamycin, however, led to donor specific cardiac allograft tolerance. This effect was accompanied by decreased anti-donor antigen cellular response and an increased percentage of spleen CD4+CD25+ T cells in recipients. Furthermore, this donor specific tolerance could be further transferred to naïve allograft recipients through injection of splenocytes, but not serum, from tolerant recipients.ConclusionCombined with immunosuppressive treatment, donor imDex can prolong cardiac allograft survival and induce donor specific allograft tolerance.

show abstract

Section: Introductionmentioning

confidence: 99%

Tolerance Induction by Exosomes from Immature Dendritic Cells and Rapamycin in a Mouse Cardiac Allograft Model

Yang

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…11,12 Recent studies have focused on the prospective value of tol-DCs to induce clinical organ graft tolerance and to prolong graft survival. [13][14][15] Here, we provide an overview of the characteristics of tol-DCs, describe their biological functions and highlight recent advances that may yield DC-based therapeutic opportunities.…”

Section: Introductionmentioning

confidence: 99%

Tolerogenic dendritic cells and their applications in transplantation

Shi

2014

Cell Mol Immunol

View full text Add to dashboard Cite

In transplantation immunology, the ultimate goal is always to successfully and specifically induce immune tolerance of allografts. Tolerogenic dendritic cells (tol-DCs) with immunoregulatory functions have attracted much attention as they play important roles in inducing and maintaining immune tolerance. Here, we focused on tol-DCs that have the potential to promote immune tolerance after solid-organ transplantation. We focus on their development and interactions with other regulatory cells, and we also explore various tol-DC engineering protocols. Harnessing tol-DCs represents a promising cellular therapy for promoting long-term graft functional survival in transplant recipients that will most likely be achieved in the future.

show abstract

“…In recent years, more and more studies have focused on the prospective value of dendritic cells (DCs) to induce clinical organ transplant tolerance, as well as prolong graft survival [2], [3], [4]. DCs are rare, uniquely well-equipped, functionally diverse professional antigen-presenting cells (APCs) [3].…”

Section: Introductionmentioning

confidence: 99%

Adoptive Infusion of Tolerogenic Dendritic Cells Prolongs the Survival of Pancreatic Islet Allografts: A Systematic Review of 13 Mouse and Rat Studies

Sun

Shan

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

ObjectiveThe first Phase I study of autologous tolerogenic dendritic cells (Tol-DCs) in Type 1 diabetes (T1D) patients was recently completed. Pancreatic islet transplantation is an effective therapy for T1D, and infusion of Tol-DCs can control diabetes development while promoting graft survival. In this study, we aim to systematically review islet allograft survival following infusion of Tol-DCs induced by different methods, to better understand the mechanisms that mediate this process.MethodsWe searched PubMed and Embase (from inception to February 29th, 2012) for relevant publications. Data were extracted and quality was assessed by two independent reviewers. We semiquantitatively analyzed the effects of Tol-DCs on islet allograft survival using mixed leukocyte reaction, Th1/Th2 differentiation, Treg induction, and cytotoxic T lymphocyte activity as mechanisms related-outcomes. We discussed the results with respect to possible mechanisms that promote survival.ResultsThirteen articles were included. The effects of Tol-DCs induced by five methods on allograft survival were different. Survival by each method was prolonged as follows: allopeptide-pulsed Tol-DCs (42.14±44 days), drug intervention (39 days), mesenchymal stem cell induction (23 days), genetic modification (8.99±4.75 days), and other derivation (2.61±6.98 days). The results indicate that Tol-DC dose and injection influenced graft survival. Single-dose injections of 104 Tol-DCs were the most effective for allograft survival, and multiple injections were not superior. Tol-DCs were also synergistic with immunosuppressive drugs or costimulation inhibitors. Possible mechanisms include donor specific T cell hyporesponsiveness, Th2 differentiation, Treg induction, cytotoxicity against allograft reduction, and chimerism induction.ConclusionsTol-DCs induced by five methods prolong MHC mismatched islet allograft survival to different degrees, but allopeptide-pulsed host DCs perform the best. Immunosuppressive or costimulatory blockade are synergistic with Tol-DC on graft survival. Multiple injections are not superior to single injection. Yet more rigorously designed studies with larger sample sizes are still needed in future.

show abstract

Developing Immunologic Tolerance for Transplantation at the Fetal Stage

Cited by 4 publications

References 95 publications

Tolerance Induction by Exosomes from Immature Dendritic Cells and Rapamycin in a Mouse Cardiac Allograft Model

Tolerance Induction by Exosomes from Immature Dendritic Cells and Rapamycin in a Mouse Cardiac Allograft Model

Tolerogenic dendritic cells and their applications in transplantation

Adoptive Infusion of Tolerogenic Dendritic Cells Prolongs the Survival of Pancreatic Islet Allografts: A Systematic Review of 13 Mouse and Rat Studies

Contact Info

Product

Resources

About