Induction of CD4<sup>+</sup>CD25<sup>+</sup>regulatory T cells by copolymer-I through activation of transcription factor Foxp3

Hong, Jian; Li, Ningli; Zhang, Xuejun; Zheng, Biao; Zhang, Jingwu Z.

doi:10.1073/pnas.0502187102

Cited by 257 publications

(166 citation statements)

References 46 publications

Supporting

Mentioning

156

Contrasting

Unclassified

Order By: Relevance

“…In vivo tracking of proliferation after adoptive cell transfer rather indicate that treatment led to increased frequencies of FoxP3+CD4+ regulatory T cells, which are known to play a central role in immune modulation (Chen et al, 2003;Fantini et al, 2004;Ng et al, 2013;Mohammadnia-Afrouzi et al, 2015). Similarly, it has been described that in vitro incubation of human CD4+ T cells with a random polymer found in the myelin basic protein, copolymer I, can lead to FoxP3 expression, though in a non antigen-specific manner (Hong et al, 2005). Likewise, expansion of FoxP3 regulatory cells was found to be associated with protection against diabetes induced by multimerized epitopes (Piaggio et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Immune Modulation and Prevention of Autoimmune Disease by Repeated Sequences from Parasites Linked to Self Antigens

Puentes

Dickhaut

Hofstätter

et al. 2016

J Neuroimmune Pharmacol

View full text Add to dashboard Cite

Parasite proteins containing repeats are essential invasion ligands, important for their ability to evade the host immune system and to induce immunosuppression. Here, the intrinsic suppressive potential of repetitive structures within parasite proteins was exploited to induce immunomodulation in order to establish self-tolerance in an animal model of autoimmune neurological disease.We tested the tolerogenic potential of fusion proteins containing repeat sequences of parasites linked to self-antigens. The fusion constructs consist of a recombinant protein containing repeat sequences derived from the S-antigen protein (SAg) of Plasmodium falciparum linked to a CD4 T cell epitope of myelin. They were tested for their efficacy to control the development of experimental autoimmune encephalomyelitis (EAE), In addition, we used the DO11.10 transgenic mouse model to study the immune mechanisms involved in tolerance induced by SAg fusion proteins.We found that repeated sequences of P. falciparum SAg protein linked to self-epitopes markedly protected mice from EAE. These fusion constructs were powerful tolerizing agents not only in a preventive setting but also in the treatment of ongoing disease. The tolerogenic effect was shown to be antigen-specific and strongly dependent on the physical linkage of the T cell epitope to the parasite structure and on the action of anti-inflammatory cytokines like IL-10 and TGF-β. Other mechanisms include down-regulation of TNF-α accompanied by increased numbers of FoxP3 + cells. This study describes the use of repetitive structures from parasites linked to defined T cell epitopes as an effective method to induce antigen-specific tolerance with potential applicability for the treatment and prevention of autoimmune diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Immune Modulation and Prevention of Autoimmune Disease by Repeated Sequences from Parasites Linked to Self Antigens

Puentes

Dickhaut

Hofstätter

et al. 2016

J Neuroimmune Pharmacol

View full text Add to dashboard Cite

show abstract

“…It remains unclear precisely how CD4 1 CD25 1 Foxp3 1 Treg can be expanded in an antigen-specific manner in vivo and in vitro and what conditions are required to establish the proliferation of Treg. Recent studies have shown that CD4 1 CD25 1 T cells can be expanded in vivo and in vitro upon antigen stimulation [37,38]. Moreover, CD4 1 CD25 1 Treg can be induced from CD4 1 CD25 -T cells [26,27].…”

Section: Discussionmentioning

confidence: 99%

“…SJMHE1 is 66% identical to P277, a fragment of the human HSP60, which can arrest the spontaneous diabetogenic process in NOD mice [28]. Additionally, a sequence in SJMHE1 contained a random polymer of four amino acids (GLAT) also present in myelin basic protein that has been proven to be an effective treatment for MS [38,44]. Whether SJMHE1 can be used as a peptide-based therapy for allergic and autoimmune disease treatment requires further analysis.…”

mentioning

confidence: 99%

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

et al. 2009

View full text Add to dashboard Cite

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...

show abstract

“…The D-stereoisomer of GA also effectively binds MHC class II on APCs, but does not suppress EAE suggesting there may be other mechanisms of action [73]. GA treatment may restore the function of regulatory T cells (Treg) thereby increasing suppression of autoreactive lymphocytes [74]. GA's effect on the adaptive immune system is not limited to T cell interactions, however.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Interferon Beta and Glatiramer Acetate Therapy

McGraw

Lublin

2013

Neurotherapeutics

View full text Add to dashboard Cite

Induction of CD4⁺CD25⁺regulatory T cells by copolymer-I through activation of transcription factor Foxp3

Abstract: Copolymer-I (COP-I) has unique immune regulatory properties and is a treatment option for multiple sclerosis (MS

Cited by 257 publications

References 46 publications

Immune Modulation and Prevention of Autoimmune Disease by Repeated Sequences from Parasites Linked to Self Antigens

Immune Modulation and Prevention of Autoimmune Disease by Repeated Sequences from Parasites Linked to Self Antigens

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

Interferon Beta and Glatiramer Acetate Therapy

Contact Info

Product

Resources

About

Induction of CD4+CD25+regulatory T cells by copolymer-I through activation of transcription factor Foxp3

Abstract: Copolymer-I (COP-I) has unique immune regulatory properties and is a treatment option for multiple sclerosis (MS

Cited by 257 publications

References 46 publications

Immune Modulation and Prevention of Autoimmune Disease by Repeated Sequences from Parasites Linked to Self Antigens

Immune Modulation and Prevention of Autoimmune Disease by Repeated Sequences from Parasites Linked to Self Antigens

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

Interferon Beta and Glatiramer Acetate Therapy

Contact Info

Product

Resources

About

Induction of CD4⁺CD25⁺regulatory T cells by copolymer-I through activation of transcription factor Foxp3

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