Sustained exposure to bacterial antigen induces interferon-γ-dependent T cell receptor ζ down-regulation and impaired T cell function

Noemí Bronstein-Sitton; Leonor Cohen-Daniel; Ilan Vaknin; Analía V. Ezernitchi; Benny Leshem; Amal Halabi; Yael Houri-Haddad; Eugenia Greenbaum; Zichria Zakay-Rones; Lior Shapira; Michal Baniyash

doi:10.1038/ni975

Sustained exposure to bacterial antigen induces interferon-γ-dependent T cell receptor ζ down-regulation and impaired T cell function

Noemí Bronstein-Sitton, Leonor Cohen-Daniel, Ilan Vaknin, Analía V. Ezernitchi, Benny Leshem, Amal Halabi, Yael Houri-Haddad, Eugenia Greenbaum, Zichria Zakay-Rones, Lior Shapira, Michal Baniyash^*

^*Corresponding author for this work

Department of Immunology and Cancer Research

Research output: Contribution to journal › Article › peer-review

108 Scopus citations

Abstract

T cell antigen receptor ζ chain down-regulation and impaired in vitro T cell function have been described in cancer and autoimmune and infectious diseases. However, the immunological basis for this phenomenon is unknown. Sustained exposure to antigen and chronic systemic inflammation, factors shared by the various pathologies, might account for this phenomenon. We developed an in vivo experimental system that mimics these conditions and show that sustained exposure of mice to bacterial antigens was sufficient to induce T cell antigen receptor ζ chain down-regulation and impair T cell function, provided an interferon-γ-dependent T helper type 1 immune response developed. This indicates ζ chain down-regulation could be a physiological response that attenuates an exacerbated immune response. However, it can act as a 'double-edged sword', impairing immune responses to chronic diseases.

Original language	English
Pages (from-to)	957-964
Number of pages	8
Journal	Nature Immunology
Volume	4
Issue number	10
DOIs	https://doi.org/10.1038/ni975
State	Published - 1 Oct 2003

Bibliographical note

Funding Information:
We thank N. Rosenheimer-Goudsmid for help with the FACS analysis. Supported by the Society of Research Associates of the Lautenberg Center, the Concern Foundation of Los Angeles, the Israel Academy of Sciences and Humanities, and the Joseph and Matilda Melnick Fund.

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Bronstein-Sitton, N., Cohen-Daniel, L., Vaknin, I., Ezernitchi, A. V., Leshem, B., Halabi, A., Houri-Haddad, Y., Greenbaum, E., Zakay-Rones, Z., Shapira, L., & Baniyash, M. (2003). Sustained exposure to bacterial antigen induces interferon-γ-dependent T cell receptor ζ down-regulation and impaired T cell function. Nature Immunology, 4(10), 957-964. https://doi.org/10.1038/ni975

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title = "Sustained exposure to bacterial antigen induces interferon-γ-dependent T cell receptor ζ down-regulation and impaired T cell function",

abstract = "T cell antigen receptor ζ chain down-regulation and impaired in vitro T cell function have been described in cancer and autoimmune and infectious diseases. However, the immunological basis for this phenomenon is unknown. Sustained exposure to antigen and chronic systemic inflammation, factors shared by the various pathologies, might account for this phenomenon. We developed an in vivo experimental system that mimics these conditions and show that sustained exposure of mice to bacterial antigens was sufficient to induce T cell antigen receptor ζ chain down-regulation and impair T cell function, provided an interferon-γ-dependent T helper type 1 immune response developed. This indicates ζ chain down-regulation could be a physiological response that attenuates an exacerbated immune response. However, it can act as a 'double-edged sword', impairing immune responses to chronic diseases.",

author = "Noem{\'i} Bronstein-Sitton and Leonor Cohen-Daniel and Ilan Vaknin and Ezernitchi, {Anal{\'i}a V.} and Benny Leshem and Amal Halabi and Yael Houri-Haddad and Eugenia Greenbaum and Zichria Zakay-Rones and Lior Shapira and Michal Baniyash",

note = "Funding Information: We thank N. Rosenheimer-Goudsmid for help with the FACS analysis. Supported by the Society of Research Associates of the Lautenberg Center, the Concern Foundation of Los Angeles, the Israel Academy of Sciences and Humanities, and the Joseph and Matilda Melnick Fund.",

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Bronstein-Sitton, N, Cohen-Daniel, L, Vaknin, I, Ezernitchi, AV, Leshem, B, Halabi, A, Houri-Haddad, Y, Greenbaum, E, Zakay-Rones, Z, Shapira, L & Baniyash, M 2003, 'Sustained exposure to bacterial antigen induces interferon-γ-dependent T cell receptor ζ down-regulation and impaired T cell function', Nature Immunology, vol. 4, no. 10, pp. 957-964. https://doi.org/10.1038/ni975

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AU - Bronstein-Sitton, Noemí

AU - Cohen-Daniel, Leonor

AU - Vaknin, Ilan

AU - Ezernitchi, Analía V.

AU - Leshem, Benny

AU - Halabi, Amal

AU - Houri-Haddad, Yael

AU - Greenbaum, Eugenia

AU - Zakay-Rones, Zichria

AU - Shapira, Lior

AU - Baniyash, Michal

N1 - Funding Information: We thank N. Rosenheimer-Goudsmid for help with the FACS analysis. Supported by the Society of Research Associates of the Lautenberg Center, the Concern Foundation of Los Angeles, the Israel Academy of Sciences and Humanities, and the Joseph and Matilda Melnick Fund.

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N2 - T cell antigen receptor ζ chain down-regulation and impaired in vitro T cell function have been described in cancer and autoimmune and infectious diseases. However, the immunological basis for this phenomenon is unknown. Sustained exposure to antigen and chronic systemic inflammation, factors shared by the various pathologies, might account for this phenomenon. We developed an in vivo experimental system that mimics these conditions and show that sustained exposure of mice to bacterial antigens was sufficient to induce T cell antigen receptor ζ chain down-regulation and impair T cell function, provided an interferon-γ-dependent T helper type 1 immune response developed. This indicates ζ chain down-regulation could be a physiological response that attenuates an exacerbated immune response. However, it can act as a 'double-edged sword', impairing immune responses to chronic diseases.

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Sustained exposure to bacterial antigen induces interferon-γ-dependent T cell receptor ζ down-regulation and impaired T cell function

Abstract

Bibliographical note

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