Human CD4+CD25+ Regulatory T Cells Suppress Anti‐Porcine Xenogeneic Responses

Porter, Cynthia M.; Bloom, Eda T.

doi:10.1111/j.1600-6143.2005.00972.x

Cited by 116 publications

(36 citation statements)

References 21 publications

(30 reference statements)

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“…In alloimmune responses, these FoxP3 þ Tregs have been shown to suppress CD4 þ and CD8 þ T cells as well as many other cell types including antigen-presenting cells, dendritic cells, B cells and macrophages [44][45][46]. In-vitro studies of the human T-cell responses to porcine cells have shown that CD4 þ CD25 þ Tregs were able to suppress the CD4 þ CD25 À T-cell proliferative response as well as inhibit their secretion of IFN-g, TNF-a, IL-2, IL-10 and IL-6 [47]. Wu et al [48 ] extended these findings by showing that expanded human CD4 þ CD25 þ Tregs maintained their regulatory capacity and expressed high levels of FoxP3.…”

Section: The Role Of Regulatory T Cells In Xenotransplantationmentioning

confidence: 99%

Role of regulatory T cells in xenotransplantation

O’Connell

Carrington

et al. 2010

Current Opinion in Organ Transplantation

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Section: The Role Of Regulatory T Cells In Xenotransplantationmentioning

confidence: 99%

Role of regulatory T cells in xenotransplantation

O’Connell

Carrington

et al. 2010

Current Opinion in Organ Transplantation

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“…Recent studies have shown that human Treg are capable of suppressing CD4 ? CD25 -effector T cell-mediated anti-pig cellular response in vitro (Porter and Bloom 2005;Sun et al 2010a, b;Wu et al 2008) and that adoptive transfer with in vitro polyclonally expanded human Treg prevents islet xenograft rejection by suppressing effector T cell responses (Yi et al 2012). This raises the possibility that Treg may be used therapeutically at the time of xenotransplantation to reduce the requirement of systemic immunosuppression (Muller et al 2012;O'Connell et al 2010;Muller et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Large-scale in vitro expansion of human regulatory T cells with potent xenoantigen-specific suppression

Jin

Lu²,

Zhao

et al. 2015

Cytotechnology

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Xenotransplantation is a potential solution to the organ donor shortage. Immunosuppression is required for successful application of xenotransplantation but may lead to infection and cancer. Thus, strategies for immune tolerance induction need to be developed. Polyclonal regulatory T cells (Treg) play a central role in the induction and maintenance of immune tolerance and have been shown to protect against islet xenograft rejection in vivo. However, global immune suppression may be mediated by polyclonal Treg immunotherapy and a simple method for in vitro expansion of xenoantigen-specific Treg for efficient Treg application becomes necessary. Human Treg isolated from peripheral blood mononuclear cells (PBMCs) were initially cultured with anti-CD3/CD28 beads, rapamycin and IL-2 for 7 days as polyclonal expansion. Expanded Treg were then cocultured with irradiated porcine PBMC as xenoantigen stimulation for three subsequent cycles with 7 days for each cycle in the presence of IL-2 and anti-CD3/CD28 beads. Treg phenotype and suppressive capacity were assessed after each cycle of xenoantigen stimulation. Treg expanded with one cycle of xenoantigen stimulation retained Treg suppressive phenotype but acquired no xenoantigen specificity along with poor expansion efficiency, whereas expansion with twocycle xenoantigen stimulation resulted in not only more than 800-fold Treg expansion but highly suppressive xenoantigen-specific Treg with effector Treg phenotype. However further increase of stimulation cycles resulted in reduced Treg suppressive potency. This study provides a simple approach to obtain high numbers of xenoantigen-specific Treg for immune tolerance induction in xenotransplantation.

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“…In this issue of Clinical Cancer Research, the same research team used this model to examine the capacity of human Treg to control x-GVHD in vivo (1). Previous experiments had shown the capacity of human Treg to suppress proliferation of autologous CD4 + CD25 À T cells in response to porcine xenogeneic stimulation (29). No model had yet tested the function of these cells in vivo, however.…”

mentioning

confidence: 97%