Abnormality of Oct-1 DNA binding in T cells from Sjogren's syndrome patients

Eliezer Flescher, Norma Vela-Roch, Noriyoshi Ogawa, Toru Nakabayashi, Agustin Escalante, Juan Manuel Anaya, Howard Dang, Norman Talal

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Abstract

Primary Sjogren's syndrome (SS) is an autoimmune rheumatic disease characterized by T cell hypoactivity. To understand the diminished T cell response to activation signals, we measured nucleoprotein DNA-binding activities regulating gene expression during T cell activation using the electrophoretic mobility shift assay. Peripheral blood lymphocytes from 9/19 SS patients were found to be defective in their ability to bind an octomer sequence (Oct-1). This Oct-1-binding phenotype remained stable in culture for up to 3 days prior to activation. This abnormality was not seen in resting T cells nor T cells from patients with systemic lupus erythematosus, rheumatoid arthritis (RA), or SS accompanied by RA. The SS Oct-1 DNA-binding abnormality correlated significantly with an inability of cells to exit the G(o)/G(i) cell cycle phase when stimulated in vitro. Importantly, nucleoprotein extracts showing decreased DNA-binding activity had normal amounts of Oct-1 proteins as determined by immunoprecipitation, implying a functional defect in the Oct-1 protein. Moreover, defective DNA binding was corrected by treatment with acid phosphatase.

Original languageEnglish (US)
Pages (from-to)2006-2011
Number of pages6
JournalEuropean Journal of Immunology
Volume26
Issue number9
DOIs
StatePublished - Jan 1 1996

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Keywords

  • Rheumatic disease
  • Signal transduction
  • Sjogren's syndrome
  • T lymphocyte
  • Transcription factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Flescher, E., Vela-Roch, N., Ogawa, N., Nakabayashi, T., Escalante, A., Anaya, J. M., Dang, H., & Talal, N. (1996). Abnormality of Oct-1 DNA binding in T cells from Sjogren's syndrome patients. European Journal of Immunology, 26(9), 2006-2011. https://doi.org/10.1002/eji.1830260906