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Murine hepatic stellate cells veto CD8 T cell activation by a CD54-dependent mechanism

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Murine hepatic stellate cells veto CD8 T cell activation by a CD54-dependent mechanism. / Schildberg, Frank A; Wojtalla, Alexandra; Siegmund, Sören V; Endl, Elmar; Diehl, Linda; Abdullah, Zeinab; Kurts, Christian; Knolle, Percy A.

in: HEPATOLOGY, Jahrgang 54, Nr. 1, 07.2011, S. 262-72.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Schildberg, FA, Wojtalla, A, Siegmund, SV, Endl, E, Diehl, L, Abdullah, Z, Kurts, C & Knolle, PA 2011, 'Murine hepatic stellate cells veto CD8 T cell activation by a CD54-dependent mechanism', HEPATOLOGY, Jg. 54, Nr. 1, S. 262-72. https://doi.org/10.1002/hep.24352

APA

Schildberg, F. A., Wojtalla, A., Siegmund, S. V., Endl, E., Diehl, L., Abdullah, Z., Kurts, C., & Knolle, P. A. (2011). Murine hepatic stellate cells veto CD8 T cell activation by a CD54-dependent mechanism. HEPATOLOGY, 54(1), 262-72. https://doi.org/10.1002/hep.24352

Vancouver

Schildberg FA, Wojtalla A, Siegmund SV, Endl E, Diehl L, Abdullah Z et al. Murine hepatic stellate cells veto CD8 T cell activation by a CD54-dependent mechanism. HEPATOLOGY. 2011 Jul;54(1):262-72. https://doi.org/10.1002/hep.24352

Bibtex

@article{bf9249c4e8ba483daca86494cfc6a2dd,
title = "Murine hepatic stellate cells veto CD8 T cell activation by a CD54-dependent mechanism",
abstract = "UNLABELLED: The liver has a role in T cell tolerance induction, which is mainly achieved through the functions of tolerogenic hepatic antigen-presenting cells (APCs) and regulatory T cells. Hepatic stellate cells (HSCs) are known to have various immune functions, which range from immunogenic antigen presentation to the induction of T cell apoptosis. Here we report a novel role for stellate cells in vetoing the priming of naive CD8 T cells. Murine and human HSCs and stromal cells (but not hepatocytes) prevented the activation of naive T cells by dendritic cells, artificial APCs, and phorbol 12-myristate 13-acetate/ionomycin by a cell contact-dependent mechanism. The veto function for inhibiting T cell activation was directly correlated with the activation state of HSCs and was most pronounced in HSCs from fibrotic livers. Mechanistically, high expression levels of CD54 simultaneously restricted the expression of interleukin-2 (IL-2) receptor and IL-2 in T cells, and this was responsible for the inhibitory effect because exogenous IL-2 overcame the HSC veto function.CONCLUSION: Our results demonstrate a novel function of HSCs in the local skewing of immune responses in the liver through the prevention of local stimulation of naive T cells. These results not only indicate a beneficial role in hepatic fibrosis, for which increased CD54 expression on HSCs could attenuate further T cell activation, but also identify IL-2 as a key cytokine in mediating local T cell immunity to overcome hepatic tolerance.",
keywords = "Animals, Antigen-Presenting Cells, Apoptosis, CD8-Positive T-Lymphocytes, Cell Communication, Cell Line, Cells, Cultured, Dendritic Cells, Disease Models, Animal, Hepatic Stellate Cells, Humans, Intercellular Adhesion Molecule-1, Interleukin-2, Liver Cirrhosis, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Models, Animal, T-Lymphocytes, Regulatory",
author = "Schildberg, {Frank A} and Alexandra Wojtalla and Siegmund, {S{\"o}ren V} and Elmar Endl and Linda Diehl and Zeinab Abdullah and Christian Kurts and Knolle, {Percy A}",
note = "Copyright {\textcopyright} 2011 American Association for the Study of Liver Diseases.",
year = "2011",
month = jul,
doi = "10.1002/hep.24352",
language = "English",
volume = "54",
pages = "262--72",
journal = "HEPATOLOGY",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - Murine hepatic stellate cells veto CD8 T cell activation by a CD54-dependent mechanism

AU - Schildberg, Frank A

AU - Wojtalla, Alexandra

AU - Siegmund, Sören V

AU - Endl, Elmar

AU - Diehl, Linda

AU - Abdullah, Zeinab

AU - Kurts, Christian

AU - Knolle, Percy A

N1 - Copyright © 2011 American Association for the Study of Liver Diseases.

PY - 2011/7

Y1 - 2011/7

N2 - UNLABELLED: The liver has a role in T cell tolerance induction, which is mainly achieved through the functions of tolerogenic hepatic antigen-presenting cells (APCs) and regulatory T cells. Hepatic stellate cells (HSCs) are known to have various immune functions, which range from immunogenic antigen presentation to the induction of T cell apoptosis. Here we report a novel role for stellate cells in vetoing the priming of naive CD8 T cells. Murine and human HSCs and stromal cells (but not hepatocytes) prevented the activation of naive T cells by dendritic cells, artificial APCs, and phorbol 12-myristate 13-acetate/ionomycin by a cell contact-dependent mechanism. The veto function for inhibiting T cell activation was directly correlated with the activation state of HSCs and was most pronounced in HSCs from fibrotic livers. Mechanistically, high expression levels of CD54 simultaneously restricted the expression of interleukin-2 (IL-2) receptor and IL-2 in T cells, and this was responsible for the inhibitory effect because exogenous IL-2 overcame the HSC veto function.CONCLUSION: Our results demonstrate a novel function of HSCs in the local skewing of immune responses in the liver through the prevention of local stimulation of naive T cells. These results not only indicate a beneficial role in hepatic fibrosis, for which increased CD54 expression on HSCs could attenuate further T cell activation, but also identify IL-2 as a key cytokine in mediating local T cell immunity to overcome hepatic tolerance.

AB - UNLABELLED: The liver has a role in T cell tolerance induction, which is mainly achieved through the functions of tolerogenic hepatic antigen-presenting cells (APCs) and regulatory T cells. Hepatic stellate cells (HSCs) are known to have various immune functions, which range from immunogenic antigen presentation to the induction of T cell apoptosis. Here we report a novel role for stellate cells in vetoing the priming of naive CD8 T cells. Murine and human HSCs and stromal cells (but not hepatocytes) prevented the activation of naive T cells by dendritic cells, artificial APCs, and phorbol 12-myristate 13-acetate/ionomycin by a cell contact-dependent mechanism. The veto function for inhibiting T cell activation was directly correlated with the activation state of HSCs and was most pronounced in HSCs from fibrotic livers. Mechanistically, high expression levels of CD54 simultaneously restricted the expression of interleukin-2 (IL-2) receptor and IL-2 in T cells, and this was responsible for the inhibitory effect because exogenous IL-2 overcame the HSC veto function.CONCLUSION: Our results demonstrate a novel function of HSCs in the local skewing of immune responses in the liver through the prevention of local stimulation of naive T cells. These results not only indicate a beneficial role in hepatic fibrosis, for which increased CD54 expression on HSCs could attenuate further T cell activation, but also identify IL-2 as a key cytokine in mediating local T cell immunity to overcome hepatic tolerance.

KW - Animals

KW - Antigen-Presenting Cells

KW - Apoptosis

KW - CD8-Positive T-Lymphocytes

KW - Cell Communication

KW - Cell Line

KW - Cells, Cultured

KW - Dendritic Cells

KW - Disease Models, Animal

KW - Hepatic Stellate Cells

KW - Humans

KW - Intercellular Adhesion Molecule-1

KW - Interleukin-2

KW - Liver Cirrhosis

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Models, Animal

KW - T-Lymphocytes, Regulatory

U2 - 10.1002/hep.24352

DO - 10.1002/hep.24352

M3 - SCORING: Journal article

C2 - 21488077

VL - 54

SP - 262

EP - 272

JO - HEPATOLOGY

JF - HEPATOLOGY

SN - 0270-9139

IS - 1

ER -