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Article: Antigen-induced regulatory T cells.

Vigouroux, Stephane / Yvon, Eric / Biagi, Ettore / Brenner, Malcolm K

2004 Volume 104, Issue 1, Page(s) 26–33

Abstract: ... In this review we discuss how antigen-specific regulatory T cells can be identified, the cellular and molecular ... nonspecific suppression has prompted efforts to identify and dissect antigen-specific regulatory T cells ... Regulatory T cells participate in immunologic homeostasis by active suppression of inappropriate ...

Abstract	Regulatory T cells participate in immunologic homeostasis by active suppression of inappropriate immune responses. Regulatory T lymphocytes expressing CD4 and CD25 antigens and naturally present in the peripheral blood were the first to be phenotypically characterized. However, their small number and antigen nonspecific suppression has prompted efforts to identify and dissect antigen-specific regulatory T cells. In this review we discuss how antigen-specific regulatory T cells can be identified, the cellular and molecular mechanisms underlying their induction and activity, and the challenges facing their potential clinical application.
MeSH term(s)	Animals ; Antigen-Presenting Cells/immunology ; Antigens, CD/immunology ; Cytokines/immunology ; Humans ; Immune Tolerance ; Immunophenotyping ; Lymphocyte Activation/immunology ; Receptors, Cell Surface/immunology ; Receptors, Immunologic/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes, Regulatory/immunology
Chemical Substances	Antigens, CD ; Cytokines ; Receptors, Cell Surface ; Receptors, Immunologic
Language	English
Publishing date	2004-03-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2004-01-0182
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Article: Alloantigen-Induced Regulatory T Cells Generated in Presence of Vitamin C Display Enhanced Stability of Foxp3 Expression and Promote Skin Allograft Acceptance.

Nikolouli, Eirini / Hardtke-Wolenski, Matthias / Hapke, Martin / Beckstette, Michael / Geffers, Robert / Floess, Stefan / Jaeckel, Elmar / Huehn, Jochen

Frontiers in immunology

2017 Volume 8, Page(s) 748

Abstract: Regulatory T cells (Tregs) are critical for the maintenance of immune homeostasis and ...

Abstract	Regulatory T cells (Tregs) are critical for the maintenance of immune homeostasis and self-tolerance and can be therapeutically used for prevention of unwanted immune responses such as allotransplant rejection. Tregs are characterized by expression of the transcription factor Foxp3, and recent work suggests that epigenetic imprinting of
Language	English
Publishing date	2017-06-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2017.00748
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Article: Dendritic cells in the periphery control antigen-specific natural and induced regulatory T cells.

Yamazaki, Sayuri / Morita, Akimichi

Frontiers in immunology

2013 Volume 4, Page(s) 151

Abstract: ... regulatory T cells (Natural T-regs) and inducing Foxp3 expression (Induced T-regs) in Foxp3(-) CD4(+) T cells ... T-regs from Foxp3(-) cells or expanding Natural T-regs with model-antigen delivery by anti-DC subset ... CD4(+) T cells with endogenous TGF-β and retinoic acid. In addition, antigen-presenting DCs have ...

Abstract	Dendritic cells (DCs) are specialized antigen-presenting cells that regulate both immunity and tolerance. DCs in the periphery play a key role in expanding naturally occurring Foxp3(+) CD25(+) CD4(+) regulatory T cells (Natural T-regs) and inducing Foxp3 expression (Induced T-regs) in Foxp3(-) CD4(+) T cells. DCs are phenotypically and functionally heterogeneous, and further classified into several subsets depending on distinct marker expression and their location. Recent findings indicate the presence of specialized DC subsets that act to expand Natural T-regs or induce Foxp3(+) T-regs from Foxp3(-) CD4(+) T cells. For example, two major subsets of DCs in lymphoid organs act differentially in inducing Foxp3(+) T-regs from Foxp3(-) cells or expanding Natural T-regs with model-antigen delivery by anti-DC subset monoclonal antibodies in vivo. Furthermore, DCs expressing CD103 in the intestine induce Foxp3(+) T-regs from Foxp3(-) CD4(+) T cells with endogenous TGF-β and retinoic acid. In addition, antigen-presenting DCs have a capacity to generate Foxp3(+) T-regs in the oral cavity where many antigens and commensals exist, similar to intestine and skin. In skin and skin-draining lymph nodes, at least six DC subsets have been identified, suggesting a complex DC-T-reg network. Here, we will review the specific activity of DCs in expanding Natural T-regs and inducing Foxp3(+) T-regs from Foxp3(-) precursors, and further discuss the critical function of DCs in maintaining tolerance at various locations including skin and oral cavity.
Language	English
Publishing date	2013-06-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2013.00151
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Article: Superantigen-induced regulatory T cells in vivo.

Ivars, Fredrik

Chemical immunology and allergy

2007 Volume 93, Page(s) 137–160

Abstract: ... with induced nonresponsiveness to the SAg and SAg-specific regulatory T cells (Tregs). Both CD4+CD25- and ... CD4+CD25+ Tregs are generated in SAg-induced responses. The Tregs suppress T cell activation and produce ... Subsequently, the majority of the expanded T cells are deleted and the remaining SAg-reactive cells will be ...

Abstract	Bacterial and viral superantigens (SAgs) can induce the activation of a large fraction of the T cells in an individual. The activated T cells divide and produce a strong cytokine response. Subsequently, the majority of the expanded T cells are deleted and the remaining SAg-reactive cells will be anergic and tolerant to SAg exposure. The anergic population is heterogeneous and includes both T cells with induced nonresponsiveness to the SAg and SAg-specific regulatory T cells (Tregs). Both CD4+CD25- and CD4+CD25+ Tregs are generated in SAg-induced responses. The Tregs suppress T cell activation and produce the immunosuppressive cytokines IL-10 and TGF-Beta1, thereby contributing to the SAg-specific tolerance. The similarities of immune responses induced by SAgs and conventional peptide antigens administered in the absence of adjuvants will be discussed. It is proposed that the antigen-specific tolerance induced in both situations is the consequence of T cell activation mediated by immature dendritic cells.
MeSH term(s)	Animals ; Clonal Anergy ; Cytokines/biosynthesis ; Humans ; Interleukin-10/biosynthesis ; Superantigens/immunology ; T-Lymphocytes, Regulatory/immunology
Chemical Substances	Cytokines ; Superantigens ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2007-01-04
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1660-2242
ISSN	1660-2242
DOI	10.1159/000100862
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Book ; Thesis: Human viral antigen specific induced regulatory T cells

Fischer, Annika Maria

characterization and clinical relevance

2012

Author's details	vorgelegt von Annika Maria Fischer
Language	English
Size	2 Mikrofiches, Ill., graph. Darst.
Document type	Book ; Thesis
Thesis / German Habilitation thesis	@Berlin, Humboldt-Univ., Diss., 2012
Database	Special collection on veterinary medicine and general parasitology

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Book ; Thesis: Human viral antigen specific induced regulatory T cells

Fischer, Annika Maria

characterization and clinical relevance

2012

Author's details	vorgelegt von Annika Maria Fischer
Language	English
Size	2 Mikrofiches, Ill., graph. Darst
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Humboldt-Univ., Diss.--Berlin, 2012
Database	Former special subject collection: coastal and deep sea fishing

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Article: Antigen-induced regulatory T cells in autoimmunity.

von Herrath, Matthias G / Harrison, Leonard C

Nature reviews. Immunology

2003 Volume 3, Issue 3, Page(s) 223–232

Abstract: ... of such antigen-specific T(Reg) cells, and strategies for their therapeutic induction are discussed. ... of regulatory T (T(Reg)) cells by autoantigens can suppress disease, even if the primary, initiating ... autoantigens are unknown and if inflammation is progressive. An advantage of these autoreactive T(Reg) cells is ...

Abstract	The ultimate goal of any treatment for autoimmune diseases is antigen- and/or site-specific suppression of pathology. Autoaggressive lymphocytes need to be eliminated or controlled to prevent tissue damage and halt the progression of clinical disease. Strong evidence is emerging that the induction of regulatory T (T(Reg)) cells by autoantigens can suppress disease, even if the primary, initiating autoantigens are unknown and if inflammation is progressive. An advantage of these autoreactive T(Reg) cells is their ability to act as bystander suppressors and dampen inflammation in a site-specific manner in response to cognate antigen expressed locally by affected tissues. In this review, we consider the nature and function of such antigen-specific T(Reg) cells, and strategies for their therapeutic induction are discussed.
MeSH term(s)	Animals ; Antigen Presentation ; Autoantigens/administration & dosage ; Autoantigens/immunology ; Autoimmune Diseases/immunology ; Autoimmune Diseases/therapy ; Autoimmunity/immunology ; Humans ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes, Regulatory/immunology
Chemical Substances	Autoantigens
Language	English
Publishing date	2003-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	2062776-2
ISSN	1474-1741 ; 1474-1733
ISSN (online)	1474-1741
ISSN	1474-1733
DOI	10.1038/nri1029
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Zs.MG 34: Show issues

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Article: Antigen-induced regulatory T cells in HBV chronically infected patients.

Barboza, Luisa / Salmen, Siham / Goncalves, Loredana / Colmenares, Melisa / Peterson, Darrell / Montes, Henry / Cartagirone, Raimondo / Gutiérrez, Maria del Carmen / Berrueta, Lisbeth

Virology

2007 Volume 368, Issue 1, Page(s) 41–49

Abstract: ... can be antigen-induced from peripheral mononuclear cells. Conversely, naive and naturally immune subjects ... with HBcAg, a population of CD4+FoxP3+ cells expressing phenotypic markers of both natural and induced Tregs ... induced CD4+FoxP3+IL-10+ Tregs correlated with viral load, suggesting that antigen-induced Tregs ...

Abstract	T cell response against HBV is vigorous in patients with acute hepatitis who clear the virus, whereas it is weak and narrowly focused in patients with chronic disease. We report that following incubation with HBcAg, a population of CD4+FoxP3+ cells expressing phenotypic markers of both natural and induced Tregs, can be antigen-induced from peripheral mononuclear cells. Conversely, naive and naturally immune subjects did not increase CD4+FoxP3+ Tregs following stimulation with HBcAg, supporting the idea that natural Tregs are able to respond specifically to HBV antigen. Furthermore, increased frequencies of antigen-induced CD4+FoxP3+IL-10+ Tregs correlated with viral load, suggesting that antigen-induced Tregs could contribute to an inadequate response against the virus, leading to chronic infection and support the view that specific natural Tregs may be implicated in host immune tolerance during HBV infection.
MeSH term(s)	Adult ; CD4-Positive T-Lymphocytes/chemistry ; CD4-Positive T-Lymphocytes/immunology ; Chronic Disease ; Forkhead Transcription Factors/analysis ; Hepatitis B/immunology ; Hepatitis B Core Antigens/immunology ; Hepatitis B virus/immunology ; Humans ; Interleukin-10/analysis ; Middle Aged ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes, Regulatory/immunology ; Viral Load
Chemical Substances	FOXP3 protein, human ; Forkhead Transcription Factors ; Hepatitis B Core Antigens ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2007-11-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1016/j.virol.2007.06.030
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Article ; Online: Cutting edge: Receptors for C3a and C5a modulate stability of alloantigen-reactive induced regulatory T cells.

van der Touw, William / Cravedi, Paolo / Kwan, Wing-hong / Paz-Artal, Estela / Merad, Miriam / Heeger, Peter S

Journal of immunology (Baltimore, Md. : 1950)

2013 Volume 190, Issue 12, Page(s) 5921–5925

Abstract: ... generated from peripheral CD4 T cells are susceptible to inflammation-induced reversion to pathogenic ... CD4(+)Foxp3(+) regulatory T cells (Treg) are critical regulators of immune homeostasis and ... effector T cells. Building upon our previous observations that T cell-expressed receptors for C3a (C3aR ...

Abstract	CD4(+)Foxp3(+) regulatory T cells (Treg) are critical regulators of immune homeostasis and self-tolerance. Whereas thymic-derived or natural Treg stably express Foxp3, adaptive or induced Treg (iTreg) generated from peripheral CD4 T cells are susceptible to inflammation-induced reversion to pathogenic effector T cells. Building upon our previous observations that T cell-expressed receptors for C3a (C3aR) and C5a (C5aR) drive Th1 maturation, we tested the impact of C3aR/C5aR signaling on induction and stability of alloreactive iTreg. We observed that genetic deficiency or pharmacological blockade of C3aR/C5aR signaling augments murine and human iTreg generation, stabilizes Foxp3 expression, resists iTreg conversion to IFN-γ/TNF-α-producing efffector T cells, and, as a consequence, limits the clinical expression of graft-versus-host disease. Taken together, the findings highlight the expansive role of complement as a crucial modulator of T cell alloimmunity and demonstrate proof-of-concept that targeting C3a/C3aR and C5a/C5aR interactions could facilitate iTreg-mediated tolerance to alloantigens in humans.
MeSH term(s)	Animals ; Complement C3a/immunology ; Flow Cytometry ; Gene Knockdown Techniques ; Humans ; Immunoblotting ; Isoantigens/immunology ; Lymphocyte Activation/immunology ; Mice ; Mice, Knockout ; Receptor, Anaphylatoxin C5a/immunology ; Self Tolerance/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes, Regulatory/immunology
Chemical Substances	Isoantigens ; Receptor, Anaphylatoxin C5a ; Complement C3a (80295-42-7)
Language	English
Publishing date	2013-05-20
Publishing country	United States
Document type	Journal Article ; Research Support, American Recovery and Reinvestment Act ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1300847
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Article ; Online: UVR-induced regulatory T cells switch antigen-presenting cells from a stimulatory to a regulatory phenotype.

Schwarz, Agatha / Schwarz, Thomas

The Journal of investigative dermatology

2010 Volume 130, Issue 7, Page(s) 1914–1921

Abstract: UVR-induced regulatory T cells (UVR-Treg) inhibit sensitization in an antigen-specific manner ... but induced the negative regulatory molecules B7-H3 and B7-H4 on DC. To suppress, UVR-Treg had to be activated ... The migratory behavior of UVR-Treg can be reprogrammed by antigen-presenting cells (APCs), indicating a cross ...

Abstract	UVR-induced regulatory T cells (UVR-Treg) inhibit sensitization in an antigen-specific manner. The migratory behavior of UVR-Treg can be reprogrammed by antigen-presenting cells (APCs), indicating a cross-talk between these cells. Hence, we sought to investigate whether in turn UVR-Treg can influence APCs. Bone marrow-derived dendritic cells (DCs) were co-incubated with DNFB-specific UVR-Treg. DCs were isolated, coupled with DNBS, and injected into naive mice. Contrary to untreated dinitrobenzenesulfonic acid (DNBS)-coupled DC, DCs from the cocultures failed to induce sensitization in the recipients. Antibody blocking and transwell experiments indicated that both IL-10 and cellular contact are required during the co-incubation to induce inhibition. UVR-Treg downregulated B7-2 and major histocompatibility complex class II but induced the negative regulatory molecules B7-H3 and B7-H4 on DC. To suppress, UVR-Treg had to be activated in an antigen-specific manner. However, the suppression was not antigen-specific as activated DNFB-specific UVR-Treg inhibited DCs to sensitize also against trinitrochlorobenzene. Adoptive transfer experiments revealed that injection of hapten-coupled DCs, which were co-incubated with UVR-Treg, further induced Treg in the recipients. Together, this indicates that activated UVR-Treg can alter APCs in such a way that they lose their sensitizing capacity but in turn induce Treg. Thus, UVR-Tregs switch APCs from a stimulatory to a regulatory phenotype.
MeSH term(s)	Animals ; Antigen Presentation/immunology ; Antigen Presentation/radiation effects ; Antigen-Presenting Cells/cytology ; Antigen-Presenting Cells/immunology ; Antigen-Presenting Cells/radiation effects ; Cell Communication/immunology ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Dermatitis, Contact/immunology ; Dermatitis, Contact/pathology ; Flow Cytometry ; Immunophenotyping ; Interleukin-10/genetics ; Interleukin-10/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; T-Lymphocytes, Regulatory/cytology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/radiation effects ; Ultraviolet Rays/adverse effects
Chemical Substances	Interleukin-10 (130068-27-8)
Language	English
Publishing date	2010-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1038/jid.2010.59
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