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Regulatory T cells that recognize a ubiquitous stress-inducible self-antigen are long-lived suppressors of autoimmune arthritis.

ABSTRACT: Reestablishing self-tolerance in autoimmunity is thought to depend on self-reactive regulatory T cells (Tregs). Exploiting these antigen-specific regulators is hampered by the obscure nature of disease-relevant autoantigens. We have uncovered potent disease-suppressive Tregs recognizing Heat Shock Protein (Hsp) 70 self-antigens, enabling selective activity in inflamed tissues. Hsp70 is a major contributor to the MHC class II ligandome. Here we show that a conserved Hsp70 epitope (B29) is present in murine MHC class II and that upon transfer, B29-induced CD4(+)CD25(+)Foxp3(+) T cells suppress established proteoglycan-induced arthritis in mice. These self-antigen-specific Tregs were activated in vivo, and when using Lymphocyte Activation Gene-3 as a selection marker, as few as 4,000 cells sufficed. Furthermore, depletion of transferred Tregs abrogated disease suppression. Transferred cells exhibited a stable phenotype and were found in joints and draining lymph nodes up to 2 mo after transfer. Given that (i) B29 administration by itself suppressed disease, (ii) our findings were made with wild-type (T-cell receptor nontransgenic) Tregs, and (iii) the B29 human homolog is presented by HLA class II, we are nearing translation of antigen-specific Treg activation as a promising intervention for chronic inflammatory diseases.

SUBMITTER: van Herwijnen MJ

PROVIDER: S-EPMC3435203 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Regulatory T cells that recognize a ubiquitous stress-inducible self-antigen are long-lived suppressors of autoimmune arthritis.

van Herwijnen Martijn J C MJ Wieten Lotte L van der Zee Ruurd R van Kooten Peter J PJ Wagenaar-Hilbers Josée P JP Hoek Aad A den Braber Ineke I Anderton Stephen M SM Singh Mahavir M Meiring Hugo D HD van Els Cécile A C M CA van Eden Willem W Broere Femke F

Proceedings of the National Academy of Sciences of the United States of America 20120813 35

Reestablishing self-tolerance in autoimmunity is thought to depend on self-reactive regulatory T cells (Tregs). Exploiting these antigen-specific regulators is hampered by the obscure nature of disease-relevant autoantigens. We have uncovered potent disease-suppressive Tregs recognizing Heat Shock Protein (Hsp) 70 self-antigens, enabling selective activity in inflamed tissues. Hsp70 is a major contributor to the MHC class II ligandome. Here we show that a conserved Hsp70 epitope (B29) is present ...[more]

PMID: 22891339

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Project description:BackgroundChronic illnesses, such as Rheumatoid Arthritis (RA), are a growing burden on health care systems worldwide. Self-management emphasises the patient's central role in managing their illness. This is pertinent given the majority of care is provided by the individual themselves; yet how individuals make sense of self-management in everyday life is largely unseen.ObjectiveThe purpose of this study was to capture the strengths and concerns of individuals with RA in self-managing their illness, raise awareness of their lived experience and spark a dialogue among stakeholders.MethodsA community-based participatory approach, Photovoice, was adopted. A purposive sample of participants were tasked with taking photographs to represent the challenges and solutions to living with RA. Group workshops and semi-structured interviews were conducted to facilitate reflection, dialogue and analysis. Data analysis followed Braun and Clarke's thematic analysis. Public exhibitions were held throughout the Autumn of 2019.ResultsEight women and three men (n = 11) across suburban and urban regions of Ireland were recruited (mean age 57 years, disease duration 4-21 years). Participants identified four main themes which reflected the lived experience of self-managing RA: (i) I'm Here but I'm Not, (ii) Visible Illness, (iii) Medicine in All its Forms, (iv) Mind Yourself. These themes captured the challenge of reduced agency, limited contribution and participation, and a complex relationship between visible and invisible illness. Solutions focused on improving psychological and emotional resilience, particularly through personal reflection and increased agency.ConclusionsOur findings suggest that RA is experienced as a fluid relationship between states of masking and surfacing of illness shaped by contextual and situational factors. Photovoice was a highly effective tool to capture and communicate this complexity. Supporting increased agency among individuals with RA to control the (in)visibility of illness and disability can inform the development of future self-management support.

Dataset Information

Regulatory T cells that recognize a ubiquitous stress-inducible self-antigen are long-lived suppressors of autoimmune arthritis.

Publications

Regulatory T cells that recognize a ubiquitous stress-inducible self-antigen are long-lived suppressors of autoimmune arthritis.

Similar Datasets

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