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Human regulatory T cells rapidly suppress T cell receptor-induced Ca(2+), NF-κB, and NFAT signaling in conventional T cells.

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Human regulatory T cells rapidly suppress T cell receptor-induced Ca(2+), NF-κB, and NFAT signaling in conventional T cells. / Schmidt, Angelika; Oberle, Nina; Weiss, Eva-Maria; Vobis, Diana; Frischbutter, Stefan; Baumgrass, Ria; Falk, Christine S; Haag, Mathias; Brügger, Britta; Lin, Hongying; Mayr, Georg W.; Reichardt, Peter; Gunzer, Matthias; Suri-Payer, Elisabeth; Krammer, Peter H.

In: SCI SIGNAL, Vol. 4, No. 204, 204, 2011, p. 90.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schmidt, A, Oberle, N, Weiss, E-M, Vobis, D, Frischbutter, S, Baumgrass, R, Falk, CS, Haag, M, Brügger, B, Lin, H, Mayr, GW, Reichardt, P, Gunzer, M, Suri-Payer, E & Krammer, PH 2011, 'Human regulatory T cells rapidly suppress T cell receptor-induced Ca(2+), NF-κB, and NFAT signaling in conventional T cells.', SCI SIGNAL, vol. 4, no. 204, 204, pp. 90. <http://www.ncbi.nlm.nih.gov/pubmed/22375050?dopt=Citation>

APA

Schmidt, A., Oberle, N., Weiss, E-M., Vobis, D., Frischbutter, S., Baumgrass, R., Falk, C. S., Haag, M., Brügger, B., Lin, H., Mayr, G. W., Reichardt, P., Gunzer, M., Suri-Payer, E., & Krammer, P. H. (2011). Human regulatory T cells rapidly suppress T cell receptor-induced Ca(2+), NF-κB, and NFAT signaling in conventional T cells. SCI SIGNAL, 4(204), 90. [204]. http://www.ncbi.nlm.nih.gov/pubmed/22375050?dopt=Citation

Vancouver

Schmidt A, Oberle N, Weiss E-M, Vobis D, Frischbutter S, Baumgrass R et al. Human regulatory T cells rapidly suppress T cell receptor-induced Ca(2+), NF-κB, and NFAT signaling in conventional T cells. SCI SIGNAL. 2011;4(204):90. 204.

Bibtex

@article{d5f4c6d2669c40f4a3a1e5e831a18093,
title = "Human regulatory T cells rapidly suppress T cell receptor-induced Ca(2+), NF-κB, and NFAT signaling in conventional T cells.",
abstract = "CD4(+)CD25(hi)Foxp3(+) regulatory T cells (T(regs)) are critical mediators of self-tolerance, which is crucial for the prevention of autoimmune disease, but T(regs) can also inhibit antitumor immunity. T(regs) inhibit the proliferation of CD4(+)CD25(-) conventional T cells (T(cons)), as well as the ability of these cells to produce effector cytokines; however, the molecular mechanism of suppression remains unclear. Here, we showed that human T(regs) rapidly suppressed the release of calcium ions (Ca(2+)) from intracellular stores in response to T cell receptor (TCR) activation in T(cons). The inhibition of Ca(2+) signaling resulted in decreased dephosphorylation, and thus decreased activation, of the transcription factor nuclear factor of activated T cells 1 (NFAT1) and reduced the activation of nuclear factor ?B (NF-?B). In contrast, Ca(2+)-independent events in T(cons), such as TCR-proximal signaling and activation of the transcription factor activator protein 1 (AP-1), were not affected during coculture with T(regs). Despite suppressing intracellular Ca(2+) mobilization, coculture with T(regs) did not block the generation of inositol 1,4,5-trisphosphate in TCR-stimulated T(cons). The T(reg)-induced suppression of the activity of NFAT and NF-?B and of the expression of the gene encoding the cytokine interleukin-2 was reversed in T(cons) by increasing the concentration of intracellular Ca(2+). Our results elucidate a previously unrecognized and rapid mechanism of T(reg)-mediated suppression. This increased understanding of T(reg) function may be exploited to generate possible therapies for the treatment of autoimmune diseases and cancer.",
author = "Angelika Schmidt and Nina Oberle and Eva-Maria Weiss and Diana Vobis and Stefan Frischbutter and Ria Baumgrass and Falk, {Christine S} and Mathias Haag and Britta Br{\"u}gger and Hongying Lin and Mayr, {Georg W.} and Peter Reichardt and Matthias Gunzer and Elisabeth Suri-Payer and Krammer, {Peter H}",
year = "2011",
language = "English",
volume = "4",
pages = "90",
journal = "SCI SIGNAL",
issn = "1945-0877",
publisher = "American Association for the Advancement of Science",
number = "204",

}

RIS

TY - JOUR

T1 - Human regulatory T cells rapidly suppress T cell receptor-induced Ca(2+), NF-κB, and NFAT signaling in conventional T cells.

AU - Schmidt, Angelika

AU - Oberle, Nina

AU - Weiss, Eva-Maria

AU - Vobis, Diana

AU - Frischbutter, Stefan

AU - Baumgrass, Ria

AU - Falk, Christine S

AU - Haag, Mathias

AU - Brügger, Britta

AU - Lin, Hongying

AU - Mayr, Georg W.

AU - Reichardt, Peter

AU - Gunzer, Matthias

AU - Suri-Payer, Elisabeth

AU - Krammer, Peter H

PY - 2011

Y1 - 2011

N2 - CD4(+)CD25(hi)Foxp3(+) regulatory T cells (T(regs)) are critical mediators of self-tolerance, which is crucial for the prevention of autoimmune disease, but T(regs) can also inhibit antitumor immunity. T(regs) inhibit the proliferation of CD4(+)CD25(-) conventional T cells (T(cons)), as well as the ability of these cells to produce effector cytokines; however, the molecular mechanism of suppression remains unclear. Here, we showed that human T(regs) rapidly suppressed the release of calcium ions (Ca(2+)) from intracellular stores in response to T cell receptor (TCR) activation in T(cons). The inhibition of Ca(2+) signaling resulted in decreased dephosphorylation, and thus decreased activation, of the transcription factor nuclear factor of activated T cells 1 (NFAT1) and reduced the activation of nuclear factor ?B (NF-?B). In contrast, Ca(2+)-independent events in T(cons), such as TCR-proximal signaling and activation of the transcription factor activator protein 1 (AP-1), were not affected during coculture with T(regs). Despite suppressing intracellular Ca(2+) mobilization, coculture with T(regs) did not block the generation of inositol 1,4,5-trisphosphate in TCR-stimulated T(cons). The T(reg)-induced suppression of the activity of NFAT and NF-?B and of the expression of the gene encoding the cytokine interleukin-2 was reversed in T(cons) by increasing the concentration of intracellular Ca(2+). Our results elucidate a previously unrecognized and rapid mechanism of T(reg)-mediated suppression. This increased understanding of T(reg) function may be exploited to generate possible therapies for the treatment of autoimmune diseases and cancer.

AB - CD4(+)CD25(hi)Foxp3(+) regulatory T cells (T(regs)) are critical mediators of self-tolerance, which is crucial for the prevention of autoimmune disease, but T(regs) can also inhibit antitumor immunity. T(regs) inhibit the proliferation of CD4(+)CD25(-) conventional T cells (T(cons)), as well as the ability of these cells to produce effector cytokines; however, the molecular mechanism of suppression remains unclear. Here, we showed that human T(regs) rapidly suppressed the release of calcium ions (Ca(2+)) from intracellular stores in response to T cell receptor (TCR) activation in T(cons). The inhibition of Ca(2+) signaling resulted in decreased dephosphorylation, and thus decreased activation, of the transcription factor nuclear factor of activated T cells 1 (NFAT1) and reduced the activation of nuclear factor ?B (NF-?B). In contrast, Ca(2+)-independent events in T(cons), such as TCR-proximal signaling and activation of the transcription factor activator protein 1 (AP-1), were not affected during coculture with T(regs). Despite suppressing intracellular Ca(2+) mobilization, coculture with T(regs) did not block the generation of inositol 1,4,5-trisphosphate in TCR-stimulated T(cons). The T(reg)-induced suppression of the activity of NFAT and NF-?B and of the expression of the gene encoding the cytokine interleukin-2 was reversed in T(cons) by increasing the concentration of intracellular Ca(2+). Our results elucidate a previously unrecognized and rapid mechanism of T(reg)-mediated suppression. This increased understanding of T(reg) function may be exploited to generate possible therapies for the treatment of autoimmune diseases and cancer.

M3 - SCORING: Journal article

VL - 4

SP - 90

JO - SCI SIGNAL

JF - SCI SIGNAL

SN - 1945-0877

IS - 204

M1 - 204

ER -