OP0009 Sle-related t cell autoimmunity to histones and nucleosomes is an inherent property of the normal immune system
Authors: KA Fenton, M Van Ghelue, OP Rekvig
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> 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. <h3>Objectives</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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 <i>in vivo</i> 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. <h3>Conclusion</h3> 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. <h3>References</h3> Andreassen K, Bredholt G, Moens U, Bendiksen S, Kauric G, Rekvig OP. Eur J Immunol. 1999;29:2715–28 Andreassen K, Moens U, Nossent H, Marion TN, Rekvig OP. Arthritis Rheum. 1999;42:2449–60 Moens U, Seternes OM, Hey AW, Silsand Y, Traavik T, Johansen B, Rekvig OP. Proc Natl Acad Sci USA 1995;92:12393–7 Moens U, Seternes OM, Johansen B, Rekvig OP. Virus Genes 1997;15:135–54 Rekvig OP, Andreassen K, Moens U. Scand J Rheumatol. 1998;27:1–6 Rekvig OP, Fredriksen K, Hokland K, Moens U, Traavik T, Krishnan MR, Marion T. Scand J Immunol. 1995;41:593–602 Rekvig OP, Moens U, Sundsfjord A, Bredholt G, Osei A, Haaheim H, Traavik T, Arnesen E, Haga HJ. J Clin Invest. 1997;99:2045–54