In Vitro Expanded Human CD4+CD25+ Regulatory T Cells are Potent Suppressors of T-Cell-Mediated Xenogeneic Responses

Wu, Jingjing; Yi, Shounan; Ouyang, Liang; Jimenez, Elvira; Simond, Denbigh; Wang, Wei; Wang, Yiping; Hawthorne, Wayne J.; O’Connell, Philip J.

doi:10.1097/tp.0b013e3181734793

Cited by 35 publications

(47 citation statements)

References 46 publications

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“…One hypothesis is that the process of decellularization exposes (unmasks) certain surface peptides and molecules on the scaffold that modulate the immune response (52,(53)(54)(55). Clearly, raised levels of IL-10 also raise the possibility of a response mediated by regulatory T cells which may be playing an integral role in the effects seen, as demonstrated in this study (56,57). Finally, with regard to our in vitro results, we are unable to exclude nonspecific "bystander" effects, i.e., release of cytokines through stimulation of unrelated cells, or stimulation of unrelated T cells by cytokines during an antigenspecific T-cell response.…”

Section: -47)mentioning

confidence: 59%

Immunomodulatory effect of a decellularized skeletal muscle scaffold in a discordant xenotransplantation model

Fishman

Lowdell

Urbani³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

182

137

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Decellularized (acellular) scaffolds, composed of natural extracellular matrix, form the basis of an emerging generation of tissueengineered organ and tissue replacements capable of transforming healthcare. Prime requirements for allogeneic, or xenogeneic, decellularized scaffolds are biocompatibility and absence of rejection. The humoral immune response to decellularized scaffolds has been well documented, but there is a lack of data on the cellmediated immune response toward them in vitro and in vivo. Skeletal muscle scaffolds were decellularized, characterized in vitro, and xenotransplanted. The cellular immune response toward scaffolds was evaluated by immunohistochemistry and quantified stereologically. T-cell proliferation and cytokines, as assessed by flow cytometry using carboxy-fluorescein diacetate succinimidyl ester dye and cytometric bead array, formed an in vitro surrogate marker and correlate of the in vivo host immune response toward the scaffold. Decellularized scaffolds were free of major histocompatibility complex class I and II antigens and were found to exert anti-inflammatory and immunosuppressive effects, as evidenced by delayed biodegradation time in vivo; reduced sensitized T-cell proliferative activity in vitro; reduced IL-2, IFN-γ, and raised IL-10 levels in cell-culture supernatants; polarization of the macrophage response in vivo toward an M2 phenotype; and improved survival of donor-derived xenogeneic cells at 2 and 4 wk in vivo. Decellularized scaffolds polarize host responses away from a classical TH1-proinflammatory profile and appear to down-regulate T-cell xeno responses and TH1 effector function by inducing a state of peripheral T-cell hyporesponsiveness. These results have substantial implications for the future clinical application of tissue-engineered therapies.

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Section: -47)mentioning

confidence: 59%

Immunomodulatory effect of a decellularized skeletal muscle scaffold in a discordant xenotransplantation model

Fishman

Lowdell

Urbani³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

182

137

View full text Add to dashboard Cite

show abstract

“…IL-10 is an important cytokine mediator of CD4þCD25þ Foxp3 þregulatory T cells (Tregs) mediated suppression of effector T cells proliferation [19]. Tregs plays an important role in maintaining immunologic tolerance and controlling T-cell homeostasis [20].…”

Section: Discussionmentioning

confidence: 99%

Exosomes Derived from Immature Bone Marrow Dendritic Cells Induce Tolerogenicity of Intestinal Transplantation in Rats

Yang

Shao

Jiang

et al. 2011

Journal of Surgical Research

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“…Thus, adoptive transfer of CD4 + CD25 + Tregs represents an interesting therapeutic approach in transplantation and autoimmune diseases. Recognizing the low frequency of Tregs and their high potential for adoptive immunotherapy, some protocols of Treg expansion have been developed in rodents and humans [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Adoptive transfer of CD4+CD25+ regulatory cells combined with low-dose sirolimus and anti-thymocyte globulin delays acute rejection of renal allografts in Cynomolgus monkeys

Song

et al. 2011

International Immunopharmacology

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In Vitro Expanded Human CD4+CD25+ Regulatory T Cells are Potent Suppressors of T-Cell-Mediated Xenogeneic Responses

Abstract: This study shows that expanded human Treg cells were capable of suppressing antiporcine xenogeneic responses in vitro and involve both contact dependent and cytokine mediated mechanisms.

Cited by 35 publications

References 46 publications

Immunomodulatory effect of a decellularized skeletal muscle scaffold in a discordant xenotransplantation model

Immunomodulatory effect of a decellularized skeletal muscle scaffold in a discordant xenotransplantation model

Exosomes Derived from Immature Bone Marrow Dendritic Cells Induce Tolerogenicity of Intestinal Transplantation in Rats

Adoptive transfer of CD4+CD25+ regulatory cells combined with low-dose sirolimus and anti-thymocyte globulin delays acute rejection of renal allografts in Cynomolgus monkeys

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