Emerging concepts in CD8+ T regulatory cells

Niederkorn, Jérry Y.

doi:10.1016/j.coi.2008.02.003

Cited by 68 publications

(55 citation statements)

References 36 publications

(28 reference statements)

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“…Concomitantly, the amounts of Eomes were upregulated in Irf4 -/-CD8 + T cells and Eomes inhibited IL-17 production in CD8 + T cells, in support of the previously proposed repression of the Tc17 program by a combination of Eomes and T-bet (13) and the recently published Eomes-mediated suppression of Th17 differentiation by its direct binding to the Rorc and Il17a promoters (33). Together with greatly impaired levels of RORγt and RORα, our data point to the central role of IRF4 in CD8 + T cells in balancing the levels of transcription factors responsible for Tc17, Treg (34), and CTL differentiation.…”

Section: Discussionsupporting

confidence: 63%

IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis

Huber¹,

Heink²,

et al. 2012

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Section: Discussionsupporting

confidence: 63%

IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis

Huber¹,

Heink²,

et al. 2012

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“…Peripherally induced regulatory CD8 T subsets can originate from T-cell populations without any initial regulatory capacity. They can acquire their suppressive activity under various conditions, such as by alterations in costimulatory molecule interactions (29) or following antigen recognition by unique antigen-presenting cells in so-called immune-privileged sites, such as B cells in the anterior chamber (30) or keratinocytes in hair follicles in our model. As shown here for the tolerant Des CD8 T cells, CD8 regulatory T cells display their activity mostly in an antigen-specific way (10).…”

Section: Discussionmentioning

confidence: 99%

Dickkopf-3, an immune modulator in peripheral CD8 T-cell tolerance

Papatriantafyllou

Moldenhauer²,

Ludwig

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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In healthy individuals, T cells react against incoming pathogens, but remain tolerant to self-antigens, thereby preventing autoimmune reactions. CD4 regulatory T cells are major contributors in induction and maintenance of peripheral tolerance, but a regulatory role has been also reported for several subsets of CD8 T cells. To determine the molecular basis of peripheral CD8 T-cell tolerance, we exploited a double transgenic mouse model in which CD8 T cells are neonatally tolerized following interaction with a parenchymal self-antigen. These tolerant CD8 T cells have regulatory capacity and can suppress T cells in an antigen-specific manner during adulthood. Dickkopf-3 (DKK3) was found to be expressed in the tolerant CD8 T cells and to be essential for the observed CD8 T-cell tolerance. In vitro, genetic deletion of DKK3 or blocking with antibodies restored CD8 T-cell proliferation and IL-2 production in response to the tolerizing self-antigen. Moreover, exogenous DKK3 reduced CD8 T-cell reactivity. In vivo, abrogation of DKK3 function reversed tolerance, leading to eradication of tumors expressing the target antigen and to rejection of autologous skin grafts. Thus, our findings define DKK3 as a immune modulator with a crucial role for CD8 T-cell tolerance.immune tolerance | parenchymal cells | autoimmunity

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“…CD8 + Treg cells' involvement in maintaining self-tolerance was recently identified (8,9). These cells' surface markers include CD25, CD103, and CD122 (10,11).…”

Section: Cd25mentioning

confidence: 99%

TLR2 Agonists Enhance CD8+Foxp3+ Regulatory T Cells and Suppress Th2 Immune Responses during Allergen Immunotherapy

Tsai

Yang

Niu

et al. 2010

The Journal of Immunology

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Pam3CSK4, a synthetic TLR2 ligand, has been shown to expand CD4+ regulatory T cells (Treg cells). Less is known about the function of CD8+ Treg cells than about the function of CD4+ Treg cells generated during allergen-specific immunotherapy (IT). This study investigated whether Dermatophagoides pteronyssinus-specific IT could expand the CD8+CD25+Foxp3+ Treg population and whether Pam3CSK4 could enhance the Treg population. PBMCs were isolated from healthy control subjects and from mite-sensitive asthmatic patients during IT at three specific times: before IT and 6 mo and 1 y after the maximum-tolerated dose. This study was performed without a placebo-controlled group. D. pteronyssinus-specific IT induced a significant increase in CD8+Foxp3+ Treg cells expressing intracellular IL-10 and granzyme B. Costimulation of PBMCs with Pam3CSK4 and D. pteronyssinus 2 expanded the CD8+CD25+Foxp3+ Treg population and inhibited D. pteronyssinus 2-induced IL-4 production. Pam3CSK4-treated CD8+CD25+ Treg cells directly suppressed CD4+ T cell proliferation by cell-contact inhibition. TUNEL revealed that CD8+CD25+ Treg cells, but not CD4+CD25+ Treg cells, directly induced CD4+CD45ROhi+ apoptosis. Our results provide direct evidence that Pam3CSK4 induces an immunomodulatory effect by inducing CD8+ Treg cells; therefore, it may be a good adjuvant for the treatment of mite allergies.

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Emerging concepts in CD8+ T regulatory cells

Cited by 68 publications

References 36 publications

IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis

IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis

Dickkopf-3, an immune modulator in peripheral CD8 T-cell tolerance

TLR2 Agonists Enhance CD8+Foxp3+ Regulatory T Cells and Suppress Th2 Immune Responses during Allergen Immunotherapy

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