Phenotypic and functional similarities between 5‐azacytidine‐treated t cells and a t cell subset in patients with active systemic lupus erythematosus

Bruce C. Richardson, John R. Strahler, T. Scott Pivirotto, Jawaid Quddus, Garry E. Bayliss, Laura A. Gross, Kenneth S. O'Rourke, Daniel Powers, Samir M. Hanash, Marcia A. Johnson

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163 Scopus citations

Abstract

Objective. Antigen‐specific CD4+ T cells treated with DNA methylation inhibitors become autoreactive, suggesting a novel mechanism for autoimmunity. To test whether this mechanism might be involved in systemic lupus erythematosus (SLE), phenotypic markers for the autoreactive cells were sought. Methods. Cloned normal T cells were treated with the DNA methylation inhibitor 5‐azacytidine (5‐azaC) and studied for altered gene expression. T cells from patients with active SLE were then studied for a similar change in gene expression, and cells expressing the marker were tested for autoreactivity. Results. 5‐azaC‐treated normal T cells had increased CD11a (leukocyte function‐associated antigen 1α) expression relative to other membrane molecules. A T cell subset with similar CD11a expression was found in patients with active SLE. This subset contained cells that spontaneously lysed autologous macrophages, with a specificity similar to that of 5‐azaC‐treated cells. Conclusion. The model of 5‐azaC‐induced autoreactivity may have relevance to SLE.

Original languageEnglish (US)
Pages (from-to)647-662
Number of pages16
JournalArthritis & Rheumatism
Volume35
Issue number6
DOIs
StatePublished - Jun 1992

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Richardson, B. C., Strahler, J. R., Pivirotto, T. S., Quddus, J., Bayliss, G. E., Gross, L. A., O'Rourke, K. S., Powers, D., Hanash, S. M., & Johnson, M. A. (1992). Phenotypic and functional similarities between 5‐azacytidine‐treated t cells and a t cell subset in patients with active systemic lupus erythematosus. Arthritis & Rheumatism, 35(6), 647-662. https://doi.org/10.1002/art.1780350608