Dendritic Cells and B Cells Cooperate in the Generation of CD4+CD25+FOXP3+ Allogeneic T Cells

Moore, Chris; Sauma, Daniela; Reyes, Paz; Morales, Jorge; Rosemblatt, Mario; Bono, Marı́a Rosa; Fierro, J.A.

doi:10.1016/j.transproceed.2009.12.044

Cited by 9 publications

(8 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alloreactive Treg cells are generated in the presence of allogeneic APCs, and TGF-β plus RA Based on previous studies [47,48], we designed a protocol to generate donor-reactive iTreg cell ex vivo. Purified C57BL/6 naive T cells (CD4 + CD25 − ) were cultured with BALB/c APCs in the presence of TGF-β1, IL-2, and RA (referred to as "TILRA"), and analyzed 6 days later for CD25 and Foxp3 expression.…”

Section: Resultsmentioning

confidence: 99%

“…Adoptive transfer of CD4 + CD25 + Treg cells has been successfully used in experimental immunosuppression in several animal models [52][53][54]. A previous report from our group demonstrated that allogeneic in vitro-induced Treg cells can be produced by stimulating naive T cells with allogeneic APCs in the presence of exogenous TGF-β1, IL-2, and RA [48]. In the present study, we investigated the role of RA in the generation, stability and function of allospecific Treg cells (RA-iTreg).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Alloreactive regulatory T cells generated with retinoic acid prevent skin allograft rejection

et al. 2014

View full text Add to dashboard Cite

CD4 + CD25 + Foxp3 + regulatory T (Treg) cells mediate immunological self-tolerance and suppress immune responses. Retinoic acid (RA), a natural metabolite of vitamin A, has been reported to enhance the differentiation of Treg cells in the presence of TGF-β. In this study, we show that the co-culture of naive T cells from C57BL/6 mice with allogeneic antigen-presenting cells (APCs) from BALB/c mice in the presence of TGF-β, RA, and IL-2 resulted in a striking enrichment of Foxp3 + T cells. These RA in vitro-induced regulatory T (RA-iTreg) cells did not secrete Th1-, Th2-, or Th17-related cytokines, showed a nonbiased homing potential, and expressed several cell surface molecules related to Treg-cell suppressive potential. Accordingly, these RA-iTreg cells suppressed T-cell proliferation and inhibited cytokine production by T cells in in vitro assays. Moreover, following adoptive transfer, RA-iTreg cells maintained Foxp3 expression and their suppressive capacity. Finally, RA-iTreg cells showed alloantigen-specific immunosuppressive capacity in a skin allograft model in immunodeficient mice. Altogether, these data indicate that functional and stable allogeneic-specific Treg cells may be generated using TGF-β, RA, and IL-2. Thus, RA-iTreg cells may have a potential use in the development of more effective cellular therapies in clinical transplantation. Keywords: Allogeneic regulatory T cells r Homing r Retinoic acid r Tolerance r TransplantationAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionRegulatory T (Treg) cells are responsible for inducing and maintaining peripheral tolerance [1]. Treg cells are classified into two Correspondence: Dr. Daniela Sauma e-mail: dsauma@u.uchile.cl major subpopulations: thymus-derived Treg cells, which are generated in the thymus and circulate in the periphery as functional mature Treg cells [2][3][4], and peripherally derived Treg cells, which are generated in the periphery from CD4 + CD25 − naive * These authors contributed equally to this work.C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 452-463 Immunomodulation 453T cells [5][6][7]. Treg cells target effector T cells and dendritic cells (DCs) by modulating their maturation and function through several mechanisms that suppress immune responses [8][9][10]; these include secretion of inhibitory cytokines (IL-10, IL-35, and TGF-β), granzyme/perforin-dependent mediated cytolysis, metabolic disruption [11][12][13][14][15], and the expression of LAG3 and CTLA4, which alter DC function [16,17]. In addition to the aforementioned mechanisms, Treg-cell suppressive capacity is dependent on Treg-cell migration and retention in the microenvironment where regulation is required. Differential expression patterns of chemokine receptors (such as CCR4, CCR5, and CCR9), integrins (α4β7), and selectins (CD62L) contribute to selective retention and trafficking of Treg cells and allow their appropriate localization during ...

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Alloreactive regulatory T cells generated with retinoic acid prevent skin allograft rejection

et al. 2014

View full text Add to dashboard Cite

show abstract

“…TLR-stimulated B cells secrete IFNγ, which may prime Th1 cell induction, and IL-6, which may promote or maintain the polarization of Th17 and follicular helper T (Tfh) cells. B cells were shown to be less efficient than DCs in inducing Treg cells, but the maximal Treg polarization was obtained with a mixture of B cells and DCs [20]. These observations have been made with cells from normal mice, and it would be very interesting to investigate to which extent this occurs in lupus, a disease in which each of these three T cells subsets (Th1, Th17, Tfh) are expanded [21–23].…”

Section: B Cell Vs DC Activation Of Cd4+ T Cells In Lupusmentioning

confidence: 99%

B cell contribution of the CD4⁺T cell inflammatory phenotypes in systemic lupus erythematosus

Choi

Morel

2017

Autoimmunity

View full text Add to dashboard Cite

Systemic lupus erythematosus is an autoimmune disease in which the effector molecules responsible for tissue damage are antibodies directed against a large number of self-antigens, among which nucleic acids complexed with proteins play a prominent role. These pathogenic autoantibodies are produced by plasma cells differentiated from activated autoreactive B cells, a process that requires complex interactions between multiple components of the immune systems. A key step in the activation of autoreactive B cells is provided by CD4+ T cells through cytokines and cell-to-cell contact. Lupus CD4+ T cells are autoreactive and they present an activated inflammatory phenotype that has been shown to contribute to disease. In addition to their role in antibody production, B cells have other effector functions, the most important ones being antigen presentation to and co-stimulation of CD4+ T cells, as well as the secretion of cytokines. Here we review what is known, largely based on mouse models, how these B cell effector functions contribute to the CD4+ T cell inflammatory phenotypes in lupus. When possible, we compare CD4+ T cell activation by B cells and by dendritic cells, and speculate how these interactions may contribute to the disease process.

show abstract

“…cells [78], CD11c + splenic dendritic cells [91], tolerogenic dendritic cells [92,93], and other interactions [94,95]; however, the mechanisms and the implications that these interactions may have on the regulation exerted by Breg cells remain unknown.…”

Section: Regulatory B Cells mentioning

confidence: 99%

Regulatory B Cells and Mechanisms

Rincón‐Arévalo

Sanchez-Parra

Castaño

et al. 2015

International Reviews of Immunology

View full text Add to dashboard Cite

Regulatory B cells have gained prominence in their role as modulators of the immune response against tumors, infectious diseases, and autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis, among others. The concept of regulatory B cells has been strongly associated with interleukin (IL)-10 production; however, there is growing evidence that supports the existence of other regulatory mechanisms, such as the production of transforming growth factor β (TGF-β), induced cell death of effector T cells, and the induction of CD4(+)CD25(-)Foxp3(+) regulatory T cells. The regulatory function of B cells has been associated with the presence and activation of molecules such as CD40, CD19, CD1d, and BCR. Alterations in signaling by any of these pathways leads to a marked defect in regulatory B cells and to increased clinical symptoms and proinflammatory signs, both in murine models and in autoimmune diseases in humans. B cells mainly exert their regulatory effect through the inhibition of proliferation and production of proinflammatory mediators, such as TNF-α, IFN-γ, and IL-17 by CD4(+) T cells. A better understanding of how regulatory B cells function will offer new perspectives with regard to the treatment of various human diseases.

show abstract

Dendritic Cells and B Cells Cooperate in the Generation of CD4+CD25+FOXP3+ Allogeneic T Cells

Cited by 9 publications

References 20 publications

Alloreactive regulatory T cells generated with retinoic acid prevent skin allograft rejection

Alloreactive regulatory T cells generated with retinoic acid prevent skin allograft rejection

B cell contribution of the CD4⁺T cell inflammatory phenotypes in systemic lupus erythematosus

Regulatory B Cells and Mechanisms

Contact Info

Product

Resources

About

Dendritic Cells and B Cells Cooperate in the Generation of CD4+CD25+FOXP3+ Allogeneic T Cells

Cited by 9 publications

References 20 publications

Alloreactive regulatory T cells generated with retinoic acid prevent skin allograft rejection

Alloreactive regulatory T cells generated with retinoic acid prevent skin allograft rejection

B cell contribution of the CD4+T cell inflammatory phenotypes in systemic lupus erythematosus

Regulatory B Cells and Mechanisms

Contact Info

Product

Resources

About

B cell contribution of the CD4⁺T cell inflammatory phenotypes in systemic lupus erythematosus