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Cited by 287T-cell and B-cell ImmunologyRheumatoid Arthritis Research and TherapiesCytokine Signaling Pathways and Interactions

Chronic tumor necrosis factor alters T cell responses by attenuating T cell receptor signaling

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Cope, Andrew P., Liblau, Roland S., Yang, Xiao-Dong, Congia, Mauro, Laudanna, Carlo, Schreiber, Robert D., Probert, Lesley, Kollias, George +1 more·1997·The Journal of Experimental Medicine
DOI 10.1084/jem.185.9.1573PMC PMC2196294
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Abstract

Repeated injections of adult mice with recombinant murine TNF prolong the survival of NZB/W F1 mice, and suppress type I insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. To determine whether repeated TNF injections suppress T cell function in adult mice, we studied the responses of influenza hemagglutinin-specific T cells derived from T cell receptor (HNT-TCR) transgenic mice. Treatment of adult mice with murine TNF for 3 wk suppressed a broad range of T cell responses, including proliferation and cytokine production. Furthermore, T cell responses of HNT-TCR transgenic mice also expressing the human TNF-globin transgene were markedly reduced compared to HNT-TCR single transgenic littermates, indicating that sustained p55 TNF-R signaling is sufficient to suppress T cell function in vivo. Using a model of chronic TNF exposure in vitro, we demonstrate that (a) chronic TNF effects are dose and time dependent, (b) TNF suppresses the responses of both Th1 and Th2 T helper subsets, (c) the suppressive effects of endogenous TNF produced in T cell cultures could be reversed with neutralizing monoclonal antibodies to TNF, and (d) prolonged TNF exposure attenuates T cell receptor signaling. The finding that anti-TNF treatment in vivo enhances T cell proliferative responses and cytokine production provides evidence for a novel regulatory effect of TNF on T cells in healthy laboratory mice. These effects are more pronounced in chronic inflammatory disease. In addition, our data provide a mechanism through which prolonged TNF exposure suppresses disease in animal models of autoimmunity.

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  • Inflammatory cytokines that direct T cell subtype production are altered in depressed patients.

    “Since inflammatory cytokines that direct T cell subtype production are altered in depressed patients (12–14)”

    From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [12]

    The Results section, “Prolonged TNF Exposure In Vitro Suppresses Th1 and Th2 Cell Subsets” (page unavailable), reports that TNF alters cytokine production and suppresses both Th1- and Th2-like T-cell responses. These findings concern mouse T cells, not depressed patients; our copy does not establish that the cytokines are altered in that population. (LLM, conf=0.86)

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Research works printed but not linked: 2

  1. [4]Campbell IL Iscaro A Harrison LC IFNγ and tumor necrosis factor-α cytotoxicity to murine islets of Langerhans J Immunol 1988 141 2325 2329 3139756
  2. [23]Güler ML Gorham JD Hsieh C Mackey AJ Steen RG Dietrich WF Murphy KM Genetic susceptibilty to Leishmania: IL-12 responsiveness in TH1 cell development Science (Wash DC) 1996 271 984 987 8584935

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Authors
Cope, A. P., Liblau, R. S., Yang, X.-D., Congia, M., Laudanna, C., Schreiber, R. D., Probert, L., Kollias, G., & McDevitt, H. O.
Affiliations
  • Washington University in St. Louis (US)
  • From the *Department of Microbiology and Immunology, ‡Department of Pathology, and §Department of Medicine, Stanford University School of Medicine, Stanford, California 94305; ‖Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110; and ¶Department of Molecular Genetics, Hellenic Pasteur Institute, Athens, Greece
ORCID
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
1997-05-05
Volume
185
Issue
9
Pages
1573-1584
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.185.9.1573
PMC
PMC2196294
OpenAlex
W2153191296
Cited by
287
References
38
Citations by year
2026: 3 · 2025: 4 · 2023: 4 · 2022: 1 · 2021: 8 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 11 · 2015: 6 · 2014: 11 · 2013: 8 · 2012: 13
FWCI
8.32
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • Wellcome Trust
  • Institut National de la Santé et de la Recherche Médicale
  • National Institutes of Health
  • School of Medicine, Stanford University
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
TNF-α, T cell receptor signaling, T cell suppression, TNF receptor p55, T cell proliferation, cytokine production, anti-TNF therapy, autoimmunity, type 1 diabetes, chronic inflammation
MeSH terms
Animals, Calcium, Immunosuppressive Agents, Interferon-gamma, Interleukin-2, Lymph Nodes, Lymphocyte Activation, Male, Mice, Inbred BALB C, Mice, Transgenic, Receptors, Antigen, T-Cell, Recombinant Proteins, T-Lymphocytes, Tumor Necrosis Factor-alpha, Signal Transduction, CD4-Positive T-Lymphocytes, Interleukin-4, Interleukin-10, Receptors, Tumor Necrosis Factor, Th1 Cells, Th2 Cells, Mice

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