Antigen-induced regulatory T cells

Vigouroux, Stéphane; Yvon, Eric; Biagi, Ettore; Brenner, Malcolm K.

doi:10.1182/blood-2004-01-0182

Cited by 96 publications

(67 citation statements)

References 89 publications

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“…immature APC may induce differentiation of CD4 1 and CD8 1 Treg and mediate Ag-specific peripheral tolerance [30,31]. Considering that SJMHE1-treated BMDC/Mf (but not OVA 323-339 -treated BMDC/Mf) induced CD4 1 CD25 1 Treg, we investigated BMDC/ Mf maturation following an SJMHE1 pulse.…”

Section: Sjmhe1 Failed To Induce Bmdc and M/ Maturationmentioning

confidence: 99%

CD4⁺CD25⁺ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent

et al. 2009

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Chronic schistosome infection results in the suppression of host immune responses, allowing long-term schistosome survival and restricting pathology. Current theories suggest that Treg play an important role in this regulation. However, the mechanism of Treg induction during schistosome infection is still unknown. The aim of this study was to determine the mechanism behind the induction of CD4 1 CD25 1 T cells by Schistosoma japonicum HSP60 (SjHSP60)-derived peptide SJMHE1 as well as to elucidate the cellular and molecular basis for the induction of CD4 1 CD25 1 T cells during S. japonicum infection. Mice immunized with SJMHE1 or spleen and LN cells from naïve mice pretreated with SJMHE1 in vitro all displayed an increase in CD4 1 CD25 1 T-cell populations. Release of IL-10 and TGF-b by SJMHE1 stimulation may contribute to suppression. Adoptively transferred SJMHE1-induced CD4 1 CD25 1 T cells inhibited delayed-type hypersensitivity in BALB/c mice. Additionally, SJMHE1-treated APC were tolerogenic and induced CD4 1 cells to differentiate into suppressive CD4 1 CD25 1 Treg. Furthermore, our data support a role for TLR2 in SJMHE1-mediated CD4 1 CD25 1 Treg induction. These findings provide the basis for a more complete understanding of the S. japonicum-host interactions that contribute to host homeostatic mechanisms, preventing an excessive immune response.Key words: CD4 1 CD25 1 Treg . Immunomodulation . Schistosomes . SJMHE1 . TLR2 Supporting Information available online IntroductionImmune regulation associated with protective immunity is intricate and entails the effective elimination of the pathogen without causing serious damage to the host. Conversely, effective pathogens have developed multiple mechanisms for modulating or suppressing host immunity as survival and dissemination strategies. Therefore, during the course of an infection, a struggle between host defense mechanisms and the pathogen's immunomodulatory processes results in a complex interplay that may result in pathogen eradication or damage to the host (and persistence of the pathogen). One of the survival strategies used by pathogens involves the induction of immunosuppressive cell populations, e.g. Treg [1,2]. 3052The first observations suggesting that Treg induction occurs during infections with certain pathogens were made in mice infected with Bordetella pertussis [3] and in humans infected with HCV [4] or the nematode Onchocerca volvulus [5]. More recently, Treg induction has been described in chronic infections caused by Candida albicans [6], Mycobacterium tuberculosis [7], HIV [8], Leishmania major [9], Litomosoides sigmodontis [10], and Helicobacter pylori [11]. Treg induction has also been associated with Schistosome infection. Schistosomiasis is a major human disease primarily caused by one of the three species of Schistosome endemic to parts of Asia, South America, and Africa, i.e. S. mansoni, S. haematobium, and S. japonicum. Mortality rates resulting from these types of parasitic infections are second only to malaria. Chronic schis...

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Section: Sjmhe1 Failed To Induce Bmdc and M/ Maturationmentioning

confidence: 99%

CD4⁺CD25⁺ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent

et al. 2009

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“…However, the availability of sufficient numbers of donor Treg for cell-based therapies remains limited [4]. Besides the in vitro expansion of nTreg [5], an obvious approach to solve this problem would be the de novo induction and expansion of Foxp3 1 Treg from abundant naïve CD4 1 T cells with recipient alloantigens [6,7]. Instead of mediating unspecific suppression, such alloantigen-induced Treg potentially could provide the advantage of antigen-specific regulation, thereby reducing the risk of disease relapse and infections [8].…”

Section: Introductionmentioning

confidence: 99%

Alloantigen‐specific de novo‐induced Foxp3⁺ Treg revert in vivo and do not protect from experimental GVHD

et al. 2009

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Induced antigen-specific Foxp3 1 T cells (iTreg) are being discussed as a promising alternative to polyclonal natural Foxp3 1 T cells (nTreg) for cell-based therapies, particularly to achieve transplantation tolerance. Using Foxp3eGFP-reporter mice, we here establish an efficient protocol to induce and expand alloantigen-specific iTreg from Foxp3 À CD4 1 T cells with cluster-disrupted DC. These iTreg were mainly CD62L 1 and showed efficient suppressive activity in vitro. However, in contrast to nTreg, adoptively transferred iTreg entirely failed to prevent lethal graft versus host disease (GVHD). Within irradiated recipients, the majority of adoptively transferred Foxp3 1 iTreg, but not Foxp3 1 nTreg quickly reverted to Foxp3 À CD4 1 T cells. We therefore suggest that therapeutic approaches to treat GVHD should rely on nTreg, whereas the use of de novo alloantigen-induced iTreg should be handled with caution since the stability of the regulatory phenotype of the iTreg could be of major concern.Key words: Animal models . Dendritic cells . Graft rejection . Regulatory T cells See accompanying article by commentary by Edinger IntroductionRecent advances have demonstrated that adoptively transferred exogenous Treg can inhibit graft versus host disease (GVHD) [1][2][3]. However, the availability of sufficient numbers of donor Treg for cell-based therapies remains limited [4]. Besides the in vitro expansion of nTreg [5], an obvious approach to solve this problem would be the de novo induction and expansion of Foxp3 1 Treg from abundant naïve CD4 1 T cells with recipient alloantigens [6,7]. Instead of mediating unspecific suppression, such alloantigen-induced Treg potentially could provide the advantage of antigen-specific regulation, thereby reducing the risk of disease relapse and infections [8]. Here, we present an efficient protocol to induce Foxp3 1 Treg by the use of clusterdisrupted allogeneic DC. Such allo DC-induced iTreg were functionally active in vitro and displayed a stable regulatory phenotype upon adoptive transfer into untreated syngeneic recipients. However, when used in experimental acute GVHD, these cells quickly lost Foxp3 expression and, in contrast to nTreg, did not show any protective effect. SHORT COMMUNICATION Results and discussionTo define conditions suited for the de novo induction of alloantigen-specific iTreg, we isolated Foxp3 À CD4 1 T cells from C57BL/6 Foxp3EGFP mice and co-cultured them with BM-derived allogeneic BALB/c DC that were either matured by application of LPS or via ''cluster-disruption'' (CD-DC). Disruption of the Ecadherin-mediated cell-cell contacts induces DC maturation through mechanisms distinct from TLR signaling [9]. Since antigen-loaded CD-DC have been shown to induce tolerance in mice after i.v. injection [9] we established a protocol that allowed the conversion of naïve to Foxp3 expressing cells in vitro in the presence of allogeneic but not syngeneic CD-DC. When compared with LPS-matured DC, CD-DC showed equally high expression of MHC class II, but diminished up...

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“…Advancement in immunology led to more specific characterization of these cells and now, these are classified as (1) naturally occurring CD4 + CD25 high T reg cells, (2) induced T reg cells (i.e., Tr1 and TH3 cells), and (3) CD4 + CD25 high T reg cells developing in the periphery by conversion of CD4+CD25− T cells. However, all these T reg cell populations coexist and play a vital role in immunosuppression [170][171][172][173]. In addition to this, induced CD4 + FoxP3 + T regs (Tr1 cells) also play an important role in immune tolerance [174].…”

Section: Regulatory T Cells In Tumor Microenvironmentmentioning

confidence: 99%

Adenosine as an endogenous immunoregulator in cancer pathogenesis: where to go?

Kumar

2012

Purinergic Signalling

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Cancer is a chronic disease and its pathogenesis is well correlated with infection and inflammation. Adenosine is a purine nucleoside, which is produced under metabolic stress like hypoxic conditions. Acute or chronic inflammatory conditions lead to the release of precursor adenine nucleotides (adenosine triphosphate (ATP), adenosien diphosphate (ADP) and adenosine monophosphate (AMP)) from cells, which are extracellularly catabolized into adenosine by extracellular ectonucleotidases, i.e., CD39 or nucleoside triphosphate dephosphorylase (NTPD) and CD73 or 5′-ectonucleotidase. It is now well-known that adenosine is secreted by cancer as well as immune cells during tumor pathogenesis under metabolic stress or hypoxia. Once adenosine is released into the extracellular environment, it exerts various immunomodulatory effects via adenosine receptors (A 1 , A 2A , A 2B , and A 3 ) expressed on various immune cells (i.e., macrophages, myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, dendritic cells (DCs), T cells, regulatory T cell (T regs ), etc.), which play very important roles in the pathogenesis of cancer. This review is intended to summarize the role of inflammation and adenosine in the immunopathogenesis of tumor along with regulation of tumor-specific immune response and its modulation as an adjunct approach to tumor immunotherapy.

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Antigen-induced regulatory T cells

Abstract: Regulatory T cells participate in immuno-

Cited by 96 publications

References 89 publications

CD4⁺CD25⁺ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent

CD4⁺CD25⁺ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent

Alloantigen‐specific de novo‐induced Foxp3⁺ Treg revert in vivo and do not protect from experimental GVHD

Adenosine as an endogenous immunoregulator in cancer pathogenesis: where to go?

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Antigen-induced regulatory T cells

Abstract: Regulatory T cells participate in immuno-

Cited by 96 publications

References 89 publications

CD4+CD25+ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent

CD4+CD25+ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent

Alloantigen‐specific de novo‐induced Foxp3+ Treg revert in vivo and do not protect from experimental GVHD

Adenosine as an endogenous immunoregulator in cancer pathogenesis: where to go?

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CD4⁺CD25⁺ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent

CD4⁺CD25⁺ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent

Alloantigen‐specific de novo‐induced Foxp3⁺ Treg revert in vivo and do not protect from experimental GVHD