CD4+CD25+ regulatory T cells-derived exosomes prolonged kidney allograft survival in a rat model

Yu, Xuesong; Chi-bing, Huang; Song, Bo; Xiao, Yue; Fang, Mingqi; Feng, Jiexiong; Wang, Pingxian

doi:10.1016/j.cellimm.2013.06.010

Cited by 95 publications

(102 citation statements)

References 23 publications

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“…In transplantation of the liver, kidney and other organs, as well as treatments for autoimmune diseases such as systemic lupus erythaematosus, the transfusion of CD4+CD25+ Tregs has also entered clinical applications. The transfusion of CD4+CD25+ Tregs can effectively prevent or delay the occurrence of these diseases [11, 12]. …”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effect of CD4+CD25+ Regulatory T Cells Amplified In Vitro on Experimental Autoimmune Neuritis in Rats

Wang

Cui

Qian

2018

Cell Physiol Biochem

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Background/Aims: This study aimed to explore whether the adoptive transfusion of autologous CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) has a therapeutic effect on Experimental autoimmune neuritis (EAN) model rats, and it provides new experimental and theoretical bases for the immunotherapy of Guillain-Barre syndrome (GBS). Methods: CD4+CD25+ Tregs were sorted from the spleens of rats using immunomagnetic bead separation techniques combined with flow cytometry. Their in vitro inhibitory function was determined using a lymphocyte proliferation inhibition test, and their purity was confirmed by flow cytometry. Cells were stimulated using CD3/CD28 monoclonal antibodies and were cultured in culture medium containing interleukin 2 (IL-2), transforming growth factor-β (TGF-β) and rapamycin. After 15 days of amplification, CD4+CD25+ Tregs were collected and transfused into EAN model rats. Changes in the pathology and electron microscopical morphology of rat sciatic nerves in the normal group, untreated group, low-dose group (2 × 10⁷) and high-dose group (4 × 10⁷) were observed, and the expression of CD4+CD25+FOXP3 in peripheral blood in the four groups of rats was detected by flow cytometry. Results: Compared with rats in the untreated group, rats in the treatment groups had significantly reduced infiltration of inflammatory cells in the sciatic nerve, as well as myelin and axonal damage. Additionally, the CD4+CD25+ Tregs levels in peripheral blood were significantly higher than those in the untreated group (P< 0. 05). Moreover, the therapeutic effect became more significant with an increase in the dose of adoptive transfusion. Conclusion: Adoptive transfusion of CD4+CD25+ Tregs into EAN model rats has significant therapeutic effects.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Effect of CD4+CD25+ Regulatory T Cells Amplified In Vitro on Experimental Autoimmune Neuritis in Rats

Wang

Cui

Qian

2018

Cell Physiol Biochem

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“…So far, Yu et al are the only group that have investigated the use of Treg exosomes as a therapy in a transplantation setting (52). These authors observed that the adoptive transfer of autologous rat Treg exosomes, post transplant, prolonged both survival and function of kidney allografts (52). Suggesting that Treg exosomes may represent an exciting new therapy for the induction of transplant tolerance.…”

Section: Role Of Treg Exosomes In Transplantationmentioning

confidence: 99%

“…However, DCs produce these EVs vesicles constitutively making their production easier than those from Tregs, which are isolated only after activation (65). Yu et al obtained 117 μg of exosomes from 4 × 10 9 freshly isolated rat Tregs, following activation, and the administration of 33 μg of exosomes, given over 3 time points, was sufficient to prolong the lifespan of a kidney transplant (52). Whether large quantities of pure exosomes can be isolated from human Tregs grown under GMP conditions is as yet unknown.…”

Section: Role Of Treg Exosomes In Transplantationmentioning

confidence: 99%

Regulatory T Cell-Derived Exosomes: Possible Therapeutic and Diagnostic Tools in Transplantation

et al. 2014

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Exosomes are extracellular vesicles released by many cells of the body. These small vesicles play an important part in intercellular communication both in the local environment and systemically, facilitating in the transfer of proteins, cytokines as well as miRNA between cells. The observation that exosomes isolated from immune cells such as dendritic cells (DCs) modulate the immune response has paved the way for these structures to be considered as potential immunotherapeutic reagents. Indeed, clinical trials using DC derived exosomes to facilitate immune responses to specific cancer antigens are now underway. Exosomes can also have a negative effect on the immune response and exosomes isolated from regulatory T cells (Tregs) and other subsets of T cells have been shown to have immune suppressive capacities. Here, we review what is currently known about Treg derived exosomes and their contribution to immune regulation, as well as highlighting their possible therapeutic potential for preventing graft rejection, and use as diagnostic tools to assess transplant outcome.

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“…B-cell-derived exosomes can specifically present antigens to T cells and induce T-cell responses [27]. Like other immune cells, T lymphocytes can also release exosomes [28-30]. Exosomes released by activated CD4+ T cells contain many proteins including CD4+ T cell markers such as CD4, TCR, and CD25, as well as liposomal-associated membrane protein 1 (LAMP-1) and lymphocyte function-associated antigen-1 (LFA-1), and suppress the immunity by CD8+ T lymphocytes [28].…”

Section: Discussionmentioning

confidence: 99%

Exosomes from Thymic Stromal Lymphopoietin-Activated Dendritic Cells Promote Th2 Differentiation through the OX40 Ligand

et al. 2018

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Objectives: Exosomes are extracellular vesicles released from various inflammatory cells, such as T cells, B cells, dendritic cells (DCs), and mast cells, which have been implicated in the modulation of immune response in asthma. This study aimed to investigate whether exosomes from DCs activated by thymic stromal lymphopoietin (TSLP) play a role in T-helper cell differentiation through the OX40 ligand (OX40L). Methods: Serum samples from patients with asthma were collected to measure the levels of OX40L, T-helper type 1 (Th1) cytokine interferon (IFN)-γ, and T-helper type 2 (Th2) cytokine interleukin (IL)-4 by enzyme-linked immunosorbent assay (ELISA). Exosomes were isolated from TSLP-activated DCs and co-cultured with CD4+ T cells. Western blot and ELISA assays were used to measure the levels of OX40L, IFN-γ, and IL-4 in DCs and CD4+ T cells. Flow cytometry was applied to detect Th1 and Th2 cells. Results: OX40L and IL-4 were increased and IFN-γ was decreased in serum from asthmatic patients compared with healthy controls. TSLP induced DCs to express OX40L in released exosomes, which could promote proliferation of CD4+ T cells, elevate the level of IL-4, and promote Th2 differentiation. Conclusion: Blockade of OX40L in DC-derived exosomes could inhibit exosome-mediated CD4+ T proliferation and Th2 differentiation.

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CD4+CD25+ regulatory T cells-derived exosomes prolonged kidney allograft survival in a rat model

Cited by 95 publications

References 23 publications

Therapeutic Effect of CD4+CD25+ Regulatory T Cells Amplified In Vitro on Experimental Autoimmune Neuritis in Rats

Therapeutic Effect of CD4+CD25+ Regulatory T Cells Amplified In Vitro on Experimental Autoimmune Neuritis in Rats

Regulatory T Cell-Derived Exosomes: Possible Therapeutic and Diagnostic Tools in Transplantation

Exosomes from Thymic Stromal Lymphopoietin-Activated Dendritic Cells Promote Th2 Differentiation through the OX40 Ligand

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