T cell Autoimmunity to histones and nucleosomes is a latent property of the normal immune system

Objective. 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). Methods. 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. Results. Individual in vitro-expanded histone and T-ag-specific T cells from normal individuals displayed identical TCR V-alpha and/or V-beta 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 V-beta CDR3 sequence. Conclusion. 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.