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The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8+ T cells

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The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8+ T cells. / Raczkowski, Friederike; Ritter, Josephine; Heesch, Kira; Schumacher, Valéa; Guralnik, Anna; Höcker, Lena; Raifer, Hartmann; Klein, Matthias; Bopp, Tobias; Harb, Hani; Kesper, Dörthe A; Pfefferle, Petra I; Grusdat, Melanie; Lang, Philipp A; Mittrücker, Hans-Willi; Huber, Magdalena.

In: P NATL ACAD SCI USA, Vol. 110, No. 37, 10.09.2013, p. 15019-24.

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

Harvard

Raczkowski, F, Ritter, J, Heesch, K, Schumacher, V, Guralnik, A, Höcker, L, Raifer, H, Klein, M, Bopp, T, Harb, H, Kesper, DA, Pfefferle, PI, Grusdat, M, Lang, PA, Mittrücker, H-W & Huber, M 2013, 'The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8+ T cells', P NATL ACAD SCI USA, vol. 110, no. 37, pp. 15019-24. https://doi.org/10.1073/pnas.1309378110

APA

Raczkowski, F., Ritter, J., Heesch, K., Schumacher, V., Guralnik, A., Höcker, L., Raifer, H., Klein, M., Bopp, T., Harb, H., Kesper, D. A., Pfefferle, P. I., Grusdat, M., Lang, P. A., Mittrücker, H-W., & Huber, M. (2013). The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8+ T cells. P NATL ACAD SCI USA, 110(37), 15019-24. https://doi.org/10.1073/pnas.1309378110

Vancouver

Raczkowski F, Ritter J, Heesch K, Schumacher V, Guralnik A, Höcker L et al. The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8+ T cells. P NATL ACAD SCI USA. 2013 Sep 10;110(37):15019-24. https://doi.org/10.1073/pnas.1309378110

Bibtex

@article{8c907071f51a4684ac76765ec3d16b7e,
title = "The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8+ T cells",
abstract = "Robust cytotoxic CD8(+) T-cell response is important for immunity to intracellular pathogens. Here, we show that the transcription factor IFN Regulatory Factor 4 (IRF4) is crucial for the protective CD8(+) T-cell response to the intracellular bacterium Listeria monocytogenes. IRF4-deficient (Irf4(-/-)) mice could not clear L. monocytogenes infection and generated decreased numbers of L. monocytogenes-specific CD8(+) T cells with impaired effector phenotype and function. Transfer of wild-type CD8(+) T cells into Irf4(-/-) mice improved bacterial clearance, suggesting an intrinsic defect of CD8(+) T cells in Irf4(-/-) mice. Following transfer into wild-type recipients, Irf4(-/-) CD8(+) T cells became activated and showed initial proliferation upon L. monocytogenes infection. However, these cells could not sustain proliferation, produced reduced amounts of IFN-γ and TNF-α, and failed to acquire cytotoxic function. Forced IRF4 expression in Irf4(-/-) CD8(+) T cells rescued the defect. During acute infection, Irf4(-/-) CD8(+) T cells demonstrated diminished expression of B lymphocyte-induced maturation protein-1 (Blimp-1), inhibitor of DNA binding (Id)2, and T-box expressed in T cells (T-bet), transcription factors programming effector-cell generation. IRF4 was essential for expression of Blimp-1, suggesting that altered regulation of Blimp-1 contributes to the defects of Irf4(-/-) CD8(+) T cells. Despite increased levels of B-cell lymphoma 6 (BCL-6), Eomesodermin, and Id3, Irf4(-/-) CD8(+) T cells showed impaired memory-cell formation, indicating additional functions for IRF4 in this process. As IRF4 governs B-cell and CD4(+) T-cell differentiation, the identification of its decisive role in peripheral CD8(+) T-cell differentiation, suggests a common regulatory function for IRF4 in adaptive lymphocytes fate decision.",
keywords = "Animals, Cell Differentiation, Cell Proliferation, Gene Expression, Host-Pathogen Interactions, Interferon Regulatory Factors, Listeria monocytogenes, Listeriosis, Mice, Mice, Inbred C57BL, Mice, Knockout, T-Lymphocytes, Cytotoxic, Transcription Factors",
author = "Friederike Raczkowski and Josephine Ritter and Kira Heesch and Val{\'e}a Schumacher and Anna Guralnik and Lena H{\"o}cker and Hartmann Raifer and Matthias Klein and Tobias Bopp and Hani Harb and Kesper, {D{\"o}rthe A} and Pfefferle, {Petra I} and Melanie Grusdat and Lang, {Philipp A} and Hans-Willi Mittr{\"u}cker and Magdalena Huber",
year = "2013",
month = sep,
day = "10",
doi = "10.1073/pnas.1309378110",
language = "English",
volume = "110",
pages = "15019--24",
journal = "P NATL ACAD SCI USA",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "37",

}

RIS

TY - JOUR

T1 - The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8+ T cells

AU - Raczkowski, Friederike

AU - Ritter, Josephine

AU - Heesch, Kira

AU - Schumacher, Valéa

AU - Guralnik, Anna

AU - Höcker, Lena

AU - Raifer, Hartmann

AU - Klein, Matthias

AU - Bopp, Tobias

AU - Harb, Hani

AU - Kesper, Dörthe A

AU - Pfefferle, Petra I

AU - Grusdat, Melanie

AU - Lang, Philipp A

AU - Mittrücker, Hans-Willi

AU - Huber, Magdalena

PY - 2013/9/10

Y1 - 2013/9/10

N2 - Robust cytotoxic CD8(+) T-cell response is important for immunity to intracellular pathogens. Here, we show that the transcription factor IFN Regulatory Factor 4 (IRF4) is crucial for the protective CD8(+) T-cell response to the intracellular bacterium Listeria monocytogenes. IRF4-deficient (Irf4(-/-)) mice could not clear L. monocytogenes infection and generated decreased numbers of L. monocytogenes-specific CD8(+) T cells with impaired effector phenotype and function. Transfer of wild-type CD8(+) T cells into Irf4(-/-) mice improved bacterial clearance, suggesting an intrinsic defect of CD8(+) T cells in Irf4(-/-) mice. Following transfer into wild-type recipients, Irf4(-/-) CD8(+) T cells became activated and showed initial proliferation upon L. monocytogenes infection. However, these cells could not sustain proliferation, produced reduced amounts of IFN-γ and TNF-α, and failed to acquire cytotoxic function. Forced IRF4 expression in Irf4(-/-) CD8(+) T cells rescued the defect. During acute infection, Irf4(-/-) CD8(+) T cells demonstrated diminished expression of B lymphocyte-induced maturation protein-1 (Blimp-1), inhibitor of DNA binding (Id)2, and T-box expressed in T cells (T-bet), transcription factors programming effector-cell generation. IRF4 was essential for expression of Blimp-1, suggesting that altered regulation of Blimp-1 contributes to the defects of Irf4(-/-) CD8(+) T cells. Despite increased levels of B-cell lymphoma 6 (BCL-6), Eomesodermin, and Id3, Irf4(-/-) CD8(+) T cells showed impaired memory-cell formation, indicating additional functions for IRF4 in this process. As IRF4 governs B-cell and CD4(+) T-cell differentiation, the identification of its decisive role in peripheral CD8(+) T-cell differentiation, suggests a common regulatory function for IRF4 in adaptive lymphocytes fate decision.

AB - Robust cytotoxic CD8(+) T-cell response is important for immunity to intracellular pathogens. Here, we show that the transcription factor IFN Regulatory Factor 4 (IRF4) is crucial for the protective CD8(+) T-cell response to the intracellular bacterium Listeria monocytogenes. IRF4-deficient (Irf4(-/-)) mice could not clear L. monocytogenes infection and generated decreased numbers of L. monocytogenes-specific CD8(+) T cells with impaired effector phenotype and function. Transfer of wild-type CD8(+) T cells into Irf4(-/-) mice improved bacterial clearance, suggesting an intrinsic defect of CD8(+) T cells in Irf4(-/-) mice. Following transfer into wild-type recipients, Irf4(-/-) CD8(+) T cells became activated and showed initial proliferation upon L. monocytogenes infection. However, these cells could not sustain proliferation, produced reduced amounts of IFN-γ and TNF-α, and failed to acquire cytotoxic function. Forced IRF4 expression in Irf4(-/-) CD8(+) T cells rescued the defect. During acute infection, Irf4(-/-) CD8(+) T cells demonstrated diminished expression of B lymphocyte-induced maturation protein-1 (Blimp-1), inhibitor of DNA binding (Id)2, and T-box expressed in T cells (T-bet), transcription factors programming effector-cell generation. IRF4 was essential for expression of Blimp-1, suggesting that altered regulation of Blimp-1 contributes to the defects of Irf4(-/-) CD8(+) T cells. Despite increased levels of B-cell lymphoma 6 (BCL-6), Eomesodermin, and Id3, Irf4(-/-) CD8(+) T cells showed impaired memory-cell formation, indicating additional functions for IRF4 in this process. As IRF4 governs B-cell and CD4(+) T-cell differentiation, the identification of its decisive role in peripheral CD8(+) T-cell differentiation, suggests a common regulatory function for IRF4 in adaptive lymphocytes fate decision.

KW - Animals

KW - Cell Differentiation

KW - Cell Proliferation

KW - Gene Expression

KW - Host-Pathogen Interactions

KW - Interferon Regulatory Factors

KW - Listeria monocytogenes

KW - Listeriosis

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - T-Lymphocytes, Cytotoxic

KW - Transcription Factors

U2 - 10.1073/pnas.1309378110

DO - 10.1073/pnas.1309378110

M3 - SCORING: Journal article

C2 - 23980171

VL - 110

SP - 15019

EP - 15024

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 37

ER -