Inducible costimulator-dependent IL-10 production by regulatory T cells specific for self-antigen

Kohyama, Masanori; Sugahara, Daisuke; Sugiyama, Shigeru; Yagita, Hideo; Okumura, Ko; Hozumi, Nobumichi

doi:10.1073/pnas.0400214101

Cited by 72 publications

(51 citation statements)

References 44 publications

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“…This suggested that HCV-specific T-cells are maintained at similar frequency, scope and antigenic hierarchy in chronic HCV infection as those in recovered HCV infection but are polarized toward IL-10 production rather than the IFNγ production characteristic of spontaneous HCV clearance. Possible explanations for this finding include altered T-cell maturation due to virus-induced dysfunction of antigen-presenting cells (29,50,51), viral epitope mutation (52), or altered T-cells costimulation (53)(54)(55). In the chronic phase, peripheral HCV-specific Tr1 response did not correlate with CD4 + CD25 + regulatory T-cell frequency, distinguishing Tr1 cells from CD4 + CD25 + Tregs (26,27).…”

Section: Discussionmentioning

confidence: 99%

Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis

Kaplan¹,

Ikeda²,

Li³

et al. 2008

Journal of Hepatology

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Section: Discussionmentioning

confidence: 99%

Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis

Kaplan¹,

Ikeda²,

Li³

et al. 2008

Journal of Hepatology

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“…There have been several reports indicating a role for ICOS in the induction and function of regulatory T cells (Tregs) (12)(13)(14)(15)(16)(17). In distinct mouse models such as experimental allergic encephalomyelitis (EAE) and autoimmune type 1 diabetes, blockade of ICOS signaling by anti-ICOS Abs interrupted the balance between regulatory and effector T cells and worsened disease, indicating a role for ICOS in promoting tolerance and restraining autoimmunity (12,18).…”

Section: Endritic Cells (Dc)mentioning

confidence: 99%

The Role of ICOS in Directing T Cell Responses: ICOS-Dependent Induction of T Cell Anergy by Tolerogenic Dendritic Cells

Tuettenberg¹,

Hüter²,

Hubo³

et al. 2009

The Journal of Immunology

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Tolerogenic dendritic cells (DC) play an important role in maintaining peripheral T cell tolerance in steady-state conditions through induction of anergic, IL-10-producing T cells with suppressive properties. ICOS, an activation-induced member of the CD28 family on T cells, is involved in the induction of IL-10, which itself could contribute to induction of anergy and development of suppressive T cells. Therefore, we analyzed the functional role of ICOS in the differentiation process of human CD4+ T cells upon their interaction with tolerogenic DC. We compared the functional properties of CD4+ T cells from healthy volunteers and ICOS-deficient patients after stimulation with tolerogenic DC. We report that induction of T cell anergy and suppressive capacity is completely blocked after knockdown of ICOS expression in T cells as well as after blocking of ICOS-ICOS ligand interaction in DC/T cell cocultures. Moreover, CD4+ T cells from ICOS-deficient patients were completely resistant to anergy induction and differentiation into suppressive T cells even after supplementation of IL-10. Furthermore, ICOS/ICOS ligand interaction stabilizes IL-10R expression on T cells and thus renders them sensitive to IL-10 effects. Taken together, these results indicate a crucial role for ICOS in the induction of peripheral tolerance maintained by tolerogenic DC mediated mostly via an IL-10-independent mechanism.

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“…Although MR1-restricted V␣19i T cells express low levels of CD25, they do not express FoxP3 as determined by RT-PCR of RNA from sorted cells (data not shown). ICOS is associated with IL-10 production (23) and may reflect encounter with self ligand; for instance, ICOS is expressed on naive DO11.1 transgenic T cells specific for OVA 323-339 from mice expressing high levels of OVA under control of the rat insulin promoter (24). Overall, these data are consistent with the observation that human MAIT cells have an activated/memory phenotype (2) and, furthermore, demonstrate that a T cell population phenotypically similar to V␣14i NK T cells develops in V␣19i transgenic mice on an MR1 ϩ/ϩ (but not MR1 Ϫ/Ϫ ) background and that 25-50% of this population expresses NK1.1.…”

Section: Nk11mentioning

confidence: 99%

MR1-Restricted Vα19i Mucosal-Associated Invariant T Cells Are Innate T Cells in the Gut Lamina Propria That Provide a Rapid and Diverse Cytokine Response

Kawachi

Maldonado

Strader

et al. 2006

The Journal of Immunology

161

176

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Mucosal-associated invariant T (MAIT) cells reside primarily in the gut lamina propria and require commensal flora for selection/expansion. They are restricted by the highly conserved MHC class I-related molecule MR1 and, like most NK T cells, express an invariant TCRα chain. Although they probably contribute to gut immunity, MAIT cells have not been functionally characterized because they are so rare. To create a model in which they are more abundant, we generated transgenic mice expressing only the TCRα chain (Vα19i) that defines MAIT cells. By directly comparing Vα19i transgenic mice on MR1+/+ and MR1−/− backgrounds, we were able to distinguish and characterize a population of Vα19i T cells dependent on MR1 for development. MR1-restricted Vα19i transgenic T cells recapitulate what is known about MAIT cell development. Furthermore, a relatively high proportion of transgenic MAIT cells express NK1.1, and most have a cell surface phenotype similar to that of Vα14i NK T cells. Finally, MR1-restricted Vα19i T cells secrete IFN-γ, IL-4, IL-5, and IL-10 following TCR ligation, and we provide evidence for what may be two functionally distinct MAIT cell populations. These data strongly support the idea that MAIT cells contribute to the innate immune response in the gut mucosa.

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Inducible costimulator-dependent IL-10 production by regulatory T cells specific for self-antigen

Cited by 72 publications

References 44 publications

Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis

Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis

The Role of ICOS in Directing T Cell Responses: ICOS-Dependent Induction of T Cell Anergy by Tolerogenic Dendritic Cells

MR1-Restricted Vα19i Mucosal-Associated Invariant T Cells Are Innate T Cells in the Gut Lamina Propria That Provide a Rapid and Diverse Cytokine Response

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