The apoptotic ligands TRAIL, TWEAK, and Fas ligand mediate monocyte death induced by autologous lupus T cells

Mariana J Kaplan; Emily E Lewis; Eric A Shelden; Emily Somers; Robert Pavlic; William J McCune; Bruce C Richardson

doi:10.4049/jimmunol.169.10.6020

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The apoptotic ligands TRAIL, TWEAK, and Fas ligand mediate monocyte death induced by autologous lupus T cells

Journal article

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The apoptotic ligands TRAIL, TWEAK, and Fas ligand mediate monocyte death induced by autologous lupus T cells

Mariana J Kaplan, Emily E Lewis, Eric A Shelden, Emily Somers, Robert Pavlic, William J McCune and Bruce C Richardson

The Journal of immunology (1950), Vol.169(10), pp.6020-6029

11/15/2002

DOI: https://doi.org/10.4049/jimmunol.169.10.6020

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https://hdl.handle.net/2376/116552

PMID: 12421989

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Abstract

T-Lymphocyte Subsets - immunology

Tumor Necrosis Factor-alpha - metabolism

Cytotoxicity Tests, Immunologic

Membrane Glycoproteins - metabolism

Apoptosis - drug effects

Humans

Membrane Glycoproteins - biosynthesis

Middle Aged

Tumor Necrosis Factors

Male

Monocytes - immunology

Chloroquine - pharmacology

Lymphocyte Activation - immunology

Membrane Glycoproteins - physiology

TNF-Related Apoptosis-Inducing Ligand

Lupus Erythematosus, Systemic - drug therapy

Lupus Erythematosus, Systemic - immunology

Monocytes - pathology

Adult

Female

Carrier Proteins - physiology

Carrier Proteins - biosynthesis

Cells, Cultured

Azathioprine - pharmacology

Immunity, Innate

Indomethacin - pharmacology

Fas Ligand Protein

Monocytes - drug effects

Up-Regulation - drug effects

Cytokine TWEAK

Apoptosis - immunology

Apoptosis Regulatory Proteins

Carrier Proteins - metabolism

Up-Regulation - immunology

Lymphocyte Activation - drug effects

T-Lymphocyte Subsets - metabolism

Tumor Necrosis Factor-alpha - physiology

Ligands

Hydrocortisone - pharmacology

Lupus Erythematosus, Systemic - pathology

Tumor Necrosis Factor-alpha - biosynthesis

Individuals with systemic lupus erythematosus show evidence of a significant increase in monocyte apoptosis. This process is mediated, at least in part, by an autoreactive T cell subset that kills autologous monocytes in the absence of nominal Ag. We have investigated the apoptotic pathways involved in this T cell-mediated process. Expression of the apoptotic ligands TRAIL, TNF-like weak inducer of apoptosis (TWEAK), and Fas ligand on lupus T cells was determined, and the role of these molecules in the monocyte apoptotic response was examined. We report that these apoptotic ligands mediate the autologous monocyte death induced by lupus T cells and that this cytotoxicity is associated with increased expression of these molecules on activated T cells, rather than with an increased susceptibility of lupus monocytes to apoptosis induced by these ligands. These results define novel mechanisms that contribute to increased monocyte apoptosis characterizing patients with lupus. We propose that this mechanism could provide a source of potentially antigenic material for the autoimmune response and interfere with normal clearing mechanisms.

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Title: The apoptotic ligands TRAIL, TWEAK, and Fas ligand mediate monocyte death induced by autologous lupus T cells
Creators: Mariana J Kaplan - Department of Internal Medicine, University of Michigan, 1150 West Medical Center Drive, 5220 Medical Science Research Building I, Ann Arbor, MI 48109, USA. makaplan@umich.edu
Emily E Lewis
Eric A Shelden
Emily Somers
Robert Pavlic
William J McCune
Bruce C Richardson
Publication Details: The Journal of immunology (1950), Vol.169(10), pp.6020-6029
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Grant note: AG 014783 / NIA NIH HHS AR 42525 / NIAMS NIH HHS 1P30 AR 48310 / NIAMS NIH HHS ES 011196-02 / NIEHS NIH HHS AI 42753 / NIAID NIH HHS
Identifiers: 99900547539101842
Language: English
Resource Type: Journal article