Fas (CD95)-transduced signal preferentially stimulates lupus peripheral T lymphocytes

Ken Mei Sakata, Atsuko Sakata, Norma Vela-Roch, Rolando Espinosa, Agustin Escalante, Liping Kong, Toru Nakabayashi, Jun Cheng, Norman Talal, Howard Dang

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Fas (CD95) is a cell surface receptor whose biological function in circulating peripheral T cells is not well understood. To address the question of abnormal T cell sensitivity to Fas stimulation in systemic lupus erythematosus (SLE), we studied Fas-transduced stimulation and apoptosis in peripheral blood T cells from patients with SLE and normal control. Immobilized anti-Fas monoclonal antibodies (mAb) (imCH-11; IgM type) significantly stimulated SLE T cell proliferation compared to T cells from normal donors and patients with rheumatoid arthritis (p < 0.003 and p < 0.005, respectively). The soluble form of CH-11 and other immobilized anti-Fas mAb (UB-2, ZB-4; IgG type) failed to stimulate lupus T cells while immobilized human Fas ligand did. Furthermore, imCH-11 induced IL-2 and IL-6 mRNA expression. However, imCH-11 activation failed to induce expression of the T cell activation surface molecules CD25 and CD69. Addition of exogenous ceramide, a second messenger for Fas-mediated apoptosis signaling, also induced T cell proliferation in SLE and normal controls. Moreover, fumonisin B1, a specific ceramide synthase inhibitor, and caspase inhibitors markedly suppressed imCH-11 induced T cell proliferation, suggesting that the ceramide pathway may be involved in Fas-transduced stimulation signals in SLE T cells. These results show that SLE T cells have an alteration in the Fas signal transduction pathway leading to cell proliferation. This defect may be important in Fas-mediated peripheral immune homeostasis.

Original languageEnglish (US)
Pages (from-to)2648-2660
Number of pages13
JournalEuropean Journal of Immunology
Volume28
Issue number9
DOIs
StatePublished - Sep 1998

Keywords

  • Apoptosis
  • CD95
  • Fas
  • Proliferation
  • Systemic lupus erythematosus
  • T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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