Comparative analysis of dendritic cells and anti-CD3/CD28 expanded regulatory T cells for application in transplantation

Zeng, Menghua; Guinet, Elisabeth; Nouri-Shirazi, Mahyar

doi:10.1016/j.trim.2009.07.004

Cited by 9 publications

(7 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We wondered whether an adoptive transfer of pre-activated Tregs could support endogenous Tregs in suppressing hyperinflammtion in the early phase. Since activation of purified Tregs in vitro led to pronounced apoptosis ([48] and not shown), we pre-activated Tregs in vivo by administering 250 µg of a CD28 superagonistic antibody to DEREG mice. Within three days, this treatment increased the number of splenic Foxp3 + Tregs threefold and strongly activated the cells (Figure S3A, B).…”

Section: Resultsmentioning

confidence: 99%

Foxp3+ Regulatory T Cells Are Required for Recovery from Severe Sepsis

et al. 2013

View full text Add to dashboard Cite

The role of regulatory T cells (Tregs) in bacterial sepsis remains controversial because antibody-mediated depletion experiments gave conflicting results. We employed DEREG mice (DEpletion of REGulatory T cells) and a caecal ligation and puncture model to elucidate the role of CD4+Foxp3+ Tregs in sepsis. In DEREG mice natural Tregs can be visualized easily and selectively depleted by diphtheria toxin because the animals express the diphtheria toxin receptor and enhanced green fluorescent protein as a fusion protein under the control of the foxp3 locus. We confirmed rapid Treg-activation and an increased ratio of Tregs to Teffs in sepsis. Nevertheless, 24 h after sepsis induction, Treg-depleted and control mice showed equally strong inflammation, immune cell immigration into the peritoneum and bacterial dissemination. During the first 36 h of disease survival was not influenced by Treg-depletion. Later, however, only Treg-competent animals recovered from the insult. We conclude that the suppressive capacity of Tregs is not sufficient to control overwhelming inflammation and early mortality, but is a prerequisite for the recovery from severe sepsis.

show abstract

Section: Resultsmentioning

confidence: 99%

Foxp3+ Regulatory T Cells Are Required for Recovery from Severe Sepsis

et al. 2013

View full text Add to dashboard Cite

show abstract

“…By using RNA interference to specifically silence the expressions of CD40, CD80, and CD86 in DCs, effector T cell-elicited immune response was effectively suppressed and the development of autoimmune diseases was thus avoided [22,23]. Allogeneic DCs effectively augmented the proliferation of CD4+ regulatory T cells [24,25], which in turn inhibited DC-mediated T cell immune response by suppressing proliferation, phenotypic maturation, and IL-12 production of DCs [26,27]. Our understanding of which subset of DCs is capable of inducing immune tolerance has recently been advanced by the finding that mature DCs can also induce T cell tolerance in addition to immature DCs [28,29].…”

Section: Discussionmentioning

confidence: 99%

Experimental study of the mechanism of tolerance induction in dexamethasone-treated dendritic cells

Gong

Huang

Li³

et al. 2011

Med Sci Monit

View full text Add to dashboard Cite

SummaryBackgroundThe aim of this study was to investigate the mechanisms underlying tolerance induction of dexamethasone (Dex)-treated dendritic cells (DCs).Material/MethodsWell-grown DC2.4 cells were randomly assigned to receive control, 50 μg/L, 100 μg/L, or 200 μg/L of dexamethasone and then were cultured for 6 days. The expressions of CD80, CD86, galectin-9, and PD-L1 on the surface of DC2.4 cells were analyzed with flow cytometry and the level of IL-12 secreted by DC2.4 cells was determined by ELISA. The stimulating activity of DC2.4 cells on allogeneic T cells was assessed with mixed lymphocyte reaction. Dexamethasone-treated DC2.4 cells were co-cultured with allogeneic splenic lymphocytes and the Foxp3 expression in naive T lymphocytes was determined with flow cytometry.ResultsCompared with the control group, the expressions of CD80, CD86, galectin-9, and PD-L1 on the surface of DC2.4 cells exposed to different doses of dexamethasone showed no significant changes; however, dexamethasone treatment significantly reduced IL-12 secretion and inhibited DC2.4’s stimulation on the proliferation of allogeneic T lymphocytes. Moreover, dexamethasone-treated DC2.4 cells effectively promoted FOXP3 expression in naive T lymphocytes.ConclusionsDC2.4 is a stable cell line with high expressions of CD80, CD86, and PD-L1. Dexamethasone does not significantly change the cell phenotype of DC2.4 cells, but inhibits the secretion of IL-12 cytokine and attenuates DC2.4’s stimulation of the proliferation of allogeneic T cells. Dexamethasone-treated DC2.4 cells also effectively promote FOXP3 expression in naive T lymphocytes.

show abstract

“…Hoffmann et al (2004) documented up to 40,000-fold expansion in vitro by repeatedly stimulating with CD3 and CD28 and high dose interleukin 2. While using this technique significantly inhibits graft-versus-host disease (GVHD) as well as allo- and auto-immunity (Taylor et al, 2002; Xia et al, 2006), the inhibitory effect is more pronounced when antigen-specific Tregs are administered (Masteller et al, 2005; Trenado et al, 2006; Nagahama et al, 2007; Zeng et al, 2009; Brennan et al, 2011). …”

Section: Other Cell-based Approachesmentioning

confidence: 99%

Tolerogenic therapies in transplantation

Page¹,

Dar²,

Knechtle³

2012

Front. Immun.

View full text Add to dashboard Cite

Since the concept of immunologic tolerance was discovered in the 1940s, the pursuit of tolerance induction in human transplantation has led to a rapid development of pharmacologic and biologic agents. Short-term graft survival remains an all-time high, but successful withdrawal of immunosuppression to achieve operational tolerance rarely occurs outside of liver transplantation. Collaborative efforts through the NIH sponsored Immune Tolerance Network and the European Commission sponsored Reprogramming the Immune System for Establishment of Tolerance consortia have afforded researchers opportunity to evaluate the safety and efficacy of tolerogenic strategies, investigate mechanisms of tolerance, and identify molecular and genetic markers that distinguish the tolerance phenotype. In this article, we review traditional and novel approaches to inducing tolerance for organ transplantation, with an emphasis on their translation into clinical trials.

show abstract

Comparative analysis of dendritic cells and anti-CD3/CD28 expanded regulatory T cells for application in transplantation

Cited by 9 publications

References 54 publications

Foxp3+ Regulatory T Cells Are Required for Recovery from Severe Sepsis

Foxp3+ Regulatory T Cells Are Required for Recovery from Severe Sepsis

Experimental study of the mechanism of tolerance induction in dexamethasone-treated dendritic cells

Tolerogenic therapies in transplantation

Contact Info

Product

Resources

About