Impaired Fas signaling pathway is involved in defective T cell apoptosis in autoimmune murine arthritis

J. Zhang, T. Bárdos, K. Mikecz, A. Finnegan, T. T. Glant

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Proteoglycan (PG)-induced arthritis (PGIA) is a novel autoimmune murine model for rheumatoid arthritis induced by immunization with cartilage PG in susceptible BALB/c mice. In this model, hyperproliferation of peripheral CD4+ T cells has been observed in vitro with Ag stimulation, suggesting the breakdown of peripheral tolerance. Activation-induced cell death (AICD) is a major mechanism for peripheral T cell tolerance. A defect in AICD may result in autoimmunity. We report in this study that although CD4+ T cells from both BALB/c and B6 mice, identically immunized with human cartilage PG or OVA, express equally high levels of Fas at the cell surface, CD4+ T cells from human cartilage PG-immunized BALB/c mice, which develop arthritis, fail to undergo AICD. This defect in AICD in PGIA may lead to the accumulation of autoreactive Th1 cells in the periphery. The impaired AICD in PGIA might be ascribed to an aberrant expression of Fas-like IL-1β-converting enzyme-inhibitory protein, which precludes caspase-8 activation at the death-inducing signaling complex, and subsequently suppresses the caspase cascade initiated by Fas-Fas ligand interaction. Moreover, this aberrant expression of Fas-like IL-1β-converting enzyme-inhibitory protein may also mediate TCR-induced hyperproliferation of CD4+ T cells from arthritic BALB/c mice. Our data provide the first insight into the molecular mechanism(s) of defective AICD in autoimmune arthritis.

Original languageEnglish
Pages (from-to)4981-4986
Number of pages6
JournalJournal of Immunology
Volume166
Issue number8
Publication statusPublished - Apr 15 2001

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Arthritis
Cell Death
Proteoglycans
Apoptosis
T-Lymphocytes
Cartilage
Interleukin-1
Death Domain Receptor Signaling Adaptor Proteins
Peripheral Tolerance
Th1 Cells
Fas Ligand Protein
Caspase 8
Enzymes
Caspases
Autoimmunity
Immunization
Rheumatoid Arthritis
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Impaired Fas signaling pathway is involved in defective T cell apoptosis in autoimmune murine arthritis. / Zhang, J.; Bárdos, T.; Mikecz, K.; Finnegan, A.; Glant, T. T.

In: Journal of Immunology, Vol. 166, No. 8, 15.04.2001, p. 4981-4986.

Research output: Contribution to journalArticle

Zhang, J. ; Bárdos, T. ; Mikecz, K. ; Finnegan, A. ; Glant, T. T. / Impaired Fas signaling pathway is involved in defective T cell apoptosis in autoimmune murine arthritis. In: Journal of Immunology. 2001 ; Vol. 166, No. 8. pp. 4981-4986.
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