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OP0009 Sle-related t cell autoimmunity to histones and nucleosomes is an inherent property of the normal immune system
  1. KA Fenton,
  2. M Van Ghelue,
  3. OP Rekvig
  1. Biochemical, University of Tromsoe, Tromsoe, Norway

Abstract

Background Systemic lupus erythematosus (SLE) is characterised by the generation of pathogenic B cell and T cell autoimmunity to DNA and nucleosomes. Human polyomavirus T-antigen may play a central role in initiating B cell and T cell autoimmunity to nucleosomes. Recent data demonstrate that nucleosome-T-antigen complexes stimulate nucleosome-specific B cells and T-antigen specific T cells through a hapten-carrier-like process, also indirectly resulting in termination of non-responsiveness of histone-specific T cells. This process is relevant to both SLE and normal individuals.

Objectives This work focuses on whether immune (T-antigen specific) and autoimmune (histone-specific) T cells from normal individuals share functional, structural and genetic characteristics with those deriving from SLE.

Methods Histone-specific T cell clones were generated by stimulation of peripheral blood mononuclear cells with nucleosome-T-antigen complexes and subsequently maintained by pure histones. T-antigen specific T cell clones were initiated and maintained by polyomavirus T-antigen. The frequencies of circulating T cells specific for these antigens were determined in healthy individuals and SLE patients by limiting dilution of blood mononuclear cells. T cell receptor gene usage and structure of their variable regions were determined by cDNA sequencing. The sequences were compared between the T cell populations, and between normal and SLE subjects for both T-antigen and histone specificity.

Results The frequencies of circulating T-antigen- or histone-specific T cells in normal individuals were similar to those of SLE patients. Some of the histone-specific T cells, derived from normal individuals, were clonally expanded, indicating that these cells are functionally activated in vivo in healthy individuals. Although heterogeneous for variable region structure and gene usage, histone specific T cells from healthy individuals and SLE patients selected glutamic and/or aspartic acids at position 99 and 100 of the Vb-CDR3.

Conclusion Autoimmune T cells induced among peripheral blood mononuclear cells from normal individuals were highly similar to those from SLE, demonstrating that T cell autoimmunity to nucleosomes is an inherent property of the normal immune system.

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