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Cited by 298Immunotherapy and Immune ResponsesT-cell and B-cell ImmunologyLiver physiology and pathology

Induction of cytokine production in naive CD4+ T cells by antigen-presenting murine liver sinusoidal endothelial cells but failure to induce differentiation toward Th1 cells☆, ☆☆

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KNOLLE, P, SCHMITT, E, JIN, S, GERMANN, T, DUCHMANN, R, HEGENBARTH, S, GERKEN, G, LOHSE, A·1999·Gastroenterology
DOI 10.1016/s0016-5085(99)70508-1
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Abstract

Background & aims Murine liver sinusoidal endothelial cells (LSECs) constitutively express accessory molecules and can present antigen to memory Th1 CD4(+) T cells. Using a T-cell receptor transgenic mouse line, we addressed the question whether LSECs can prime naive CD4(+) T cells. Methods Purified LSECs were investigated for their ability to induce activation and differentiation of naive CD4(+) T cells in comparison with bone marrow-derived antigen-presenting cells and macrovascular endothelial cells. Activation of T cells was determined by cytokine production. LSECs were further studied for expression of interleukin (IL)-12 by reverse-transcription polymerase chain reaction, and the unique phenotype of LSECs was determined by flow cytometry. Results We provide evidence that antigen-presenting LSECs can activate naive CD62Lhigh CD4(+) T cells. Activation of naive CD4(+) T cells by LSECs occurred in the absence of IL-12. In contrast, macrovascular endothelial cells from aorta could not activate naive CD4(+) T cells. The unique functional characteristics of microvascular LSECs together with a unique phenotype (CD4(+), CD11b+, CD11c+, CD80(+), CD86(+)) make these cells different from macrovascular endothelial cells. Furthermore, LSECs did not require in vitro maturation to activate naive CD4(+) T cells. Most importantly, LSECs failed to induce differentiation toward Th1 cells, whereas conventional antigen-presenting cell populations induced a Th1 phenotype in activated CD4(+) T cells. Upon restimulation, CD4(+) T cells, which were primed by antigen-presenting LSECs, expressed interferon gamma, IL-4, and IL-10, which is consistent with a Th0 phenotype. Exogenous cytokines (IL-1beta, IL-12, or IL-18) present during T-cell priming by antigen-presenting LSECs could not induce a Th1 phenotype, but neutralization of endogenously produced IL-4 during T-cell priming led to a reduced expression of IL-4 and IL-10 by CD4(+) T cells upon restimulation. The addition of spleen cells to cocultures of LSECs and naive CD4(+) T cells during T-cell priming led to differentiation of T cells toward a Th1 phenotype. Conclusions The ability of antigen-presenting LSECs to induce cytokine expression in naive CD4(+) T cells and their failure to induce differentiation toward a Th1 phenotype may contribute to the unique hepatic microenvironment that is known to promote tolerance.

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  • Cytokines secreted by Th17 cells activate hepatic macrophages to produce innate proinflammatory cytokines including IL6, IL1β and TNFα, as well as the major fibrogenic cytokine TGF-β1.

    “Cytokines secreted by Th17 cells activate hepatic macrophages to produce innate proinflammatory cytokines including IL6, IL1β and TNFα, as well as the major fibrogenic cytokine TGF-β1 (33).”

    From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [33]

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Authors
KNOLLE, P., SCHMITT, E., JIN, S., GERMANN, T., DUCHMANN, R., HEGENBARTH, S., GERKEN, G., & LOHSE, A.
Affiliations
  • Heidelberg University (DE)
  • Johannes Gutenberg University Mainz (DE)
  • University of Duisburg-Essen (DE)
ORCID
Venue
Gastroenterology
Publisher
Elsevier BV
Published
1999-06
Volume
116
Issue
6
Pages
1428-1440
ISSN
0016-5085 (ISSN-L)
DOI
10.1016/s0016-5085(99)70508-1
OpenAlex
W2062632117
Cited by
298
References
47
Citations by year
2026: 3 · 2025: 8 · 2024: 11 · 2023: 8 · 2022: 5 · 2021: 15 · 2020: 14 · 2019: 7 · 2018: 7 · 2017: 8 · 2016: 6 · 2015: 19 · 2014: 8 · 2013: 12 · 2012: 11
FWCI
3.51
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
liver sinusoidal endothelial cells, naive CD4+ T cells, T cell activation, Th1 differentiation, IL-12, IL-4, IL-10, interferon-gamma, antigen presentation, accessory molecules, macrovascular endothelial cells, T cell receptor transgenic mice, splenocytes, cytokine production, endogenous cytokines, T cell priming
MeSH terms
Animals, Antigen-Presenting Cells, Cell Differentiation, Cell Line, Cells, Cultured, Endothelium, Female, Interferon-gamma, Liver, Mice, Inbred BALB C, Monocytes, Phenotype, Biomarkers, CD4-Positive T-Lymphocytes, Gene Expression, Cytokines, Th1 Cells, Interleukin-12, Mice

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