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Cited by 119T-cell and B-cell ImmunologyTGF-β signaling in diseasesImmunotherapy and Immune Responses

On the mechanisms by which transforming growth factor‐β2 alters antigen‐presenting abilities of macrophages on T cell activation

Takeuchi, Masaru, Kosiewicz, Michele M., Alard, Pascale, Streilein, J. Wayne·1997·European Journal of Immunology
DOI 10.1002/eji.1830270709
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Abstract

Peritoneal exudate cells (PEC) incubated with antigen in the presence of transforming growth factor‐(TGF)‐β2 selectively suppress delayed hypersensitivity and IgG2a antibody production when injected intravenously into naive syngeneic recipients. In this study, we have examined in vitro the effects of TGF‐β2 on the antigen presenting abilities of PEC to activate DO11.10 T cells that express a transgenic T cell receptor that recognizes ovalbumin peptide fragment 323–339 in the context of I‐A d. PEC were pretreated overnight with TGF‐β2, washed extensively, then co‐cultured with DO11.10 T cells in the presence of native OVA or P323–339. We found that TGF‐β2‐treated PEC induced the production of the T helper type 2 (Th2) cytokine, interleukin‐4 (IL‐4), but unlike untreated PEC, were unable to stimulate the Th1 cytokines, IL‐2 and interferon‐γ (IFN‐γ). Furthermore, TGF‐β2 was produced in an autocrine fashion by TGF‐β2‐treated PEC and was responsible for this shift to a Th2 response. This conclusion was supported by the following results. First, TGF‐β2‐treated PEC were found to express much more TGF‐β1 and TGF‐β2 mRNA than untreated PEC. Second, TGF‐β2‐treated PEC secreted large amounts of TGF‐β including its mature form. Third, addition of neutralizing anti‐TGF‐β2 antibodies, but not neutralizing anti‐TGF‐β1 antibodies, restored the ability of antigen‐pulsed, TGF‐β2‐pretreated PEC to stimulate DO11.10 T cells to secrete IL‐2 and IFN‐γ. These results indicate that antigen‐presenting cells that encounter antigen in a TGF‐β‐enriched environment (e.g., in the eye) shift responding naive T cells toward Th2 responses by producing TGF‐β during antigen presentation.

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  • TGF-β lowers reactive oxygen species and nitric oxide, which macrophages need for their destructive functions.

    “TGF-β also suppresses reactive oxygen species and NO production, which is required for the destructive properties of macrophages178,179.”

    From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [178]

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Authors
Takeuchi, M., Kosiewicz, M. M., Alard, P., & Streilein, J. W.
Affiliations
Harvard University (US)
Corresponding author
Streilein, J. Wayne
ORCID
Venue
European Journal of Immunology
Publisher
Wiley
Published
1997-07
Volume
27
Issue
7
Pages
1648-1656
ISSN
  • 0014-2980 (ISSN-L)
  • 1521-4141
DOI
10.1002/eji.1830270709
OpenAlex
W1986725618
Cited by
119
References
43
Citations by year
2024: 2 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 2 · 2018: 1 · 2017: 3 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 2
FWCI
6.11
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 3067 d)
Locations
  • European Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Eye Institute (EY 05678)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
transforming growth factor-beta2, antigen presentation, macrophages, T cell activation, Th2 immune response, Th1 response, IL-4, interferon-gamma, interleukin-2, ovalbumin peptide, peritoneal exudate cells, delayed-type hypersensitivity, TGF-β1
MeSH terms
Animals, Antibodies, Antigen-Presenting Cells, Cell Differentiation, Cell-Free System, Growth Inhibitors, Lymphocyte Activation, Male, Mice, Inbred BALB C, Mice, Transgenic, Ovalbumin, RNA, Messenger, T-Lymphocytes, Immunodominant Epitopes, Cytokines, Transforming Growth Factor beta, Macrophages, Peritoneal, Mice

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