Dr. Andreassen and Ms Bendiksen contributed equally to this work.
T cell autoimmunity to histones and nucleosomes is a latent property of the normal immune system
Article first published online: 8 MAY 2002
Copyright © 2002 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 46, Issue 5, pages 1270–1281, May 2002
How to Cite
Andreassen, K., Bendiksen, S., Kjeldsen, E., Van Ghelue, M., Moens, U., Arnesen, E. and Rekvig, O. P. (2002), T cell autoimmunity to histones and nucleosomes is a latent property of the normal immune system. Arthritis & Rheumatism, 46: 1270–1281. doi: 10.1002/art.10254
- Issue published online: 8 MAY 2002
- Article first published online: 8 MAY 2002
- Manuscript Accepted: 11 JAN 2002
- Manuscript Received: 20 JUN 2001
- Lion's Red Feather
- Norwegian Research Council
- Oslo Sanitetsforening
Investigators in this study undertook to determine whether in vitro antigen-responsive immune (polyomavirus T antigen [T-ag]– specific) and autoimmune (histone-specific) T cells from normal individuals share structural and genetic characteristics with those from patients with systemic lupus erythematosus (SLE).
Histone-specific T cells were generated by stimulation of peripheral blood mononuclear cells (PBMCs) with nucleosome–T-ag complexes and were subsequently maintained by pure histones. T-ag–specific T cell clones were initiated and maintained by T-ag. The frequencies of circulating histone- and T-ag–specific T cells were determined in healthy individuals and in SLE patients by limiting dilution of PBMCs. T cell receptor (TCR) gene usage and variable-region structures were determined by complementary DNA sequencing. These sequences were compared between T-ag– and histone-specific T cells and between normal individuals and SLE patients for each specificity.
Individual in vitro–expanded histone- and T-ag–specific T cells from normal individuals displayed identical TCR Vα and/or Vβ chain third complementarity-determining region (CDR3) sequences, indicating that they were clonally expanded in vivo. The frequencies of in vitro antigen-responsive T-ag– or histone-specific T cells from normal individuals were similar to those from SLE patients. Although heterogeneous for variable-region structure and gene usage, histone-specific T cells from healthy individuals and SLE patients selected aspartic and/or glutamic acids at positions 99 and/or 100 of the Vβ CDR3 sequence.
Autoimmune T cells from healthy individuals can be activated by nucleosome– T-ag complexes and maintained by histones in vitro. Such T cells possessed TCR structures similar to those from SLE patients, demonstrating that T cell autoimmunity to nucleosomes may be a latent property of the normal immune system.