title: Implications of the parent-into-F1 model for human lupus pathogenesis: roles for cytotoxic T lymphocytes and viral pathogens.
abstract: OBJECTIVE
  The central role of CD4 T cells in lupus pathogenesis is well recognized; however, the mechanism by which CD4 T cells lose tolerance and promote humoral autoimmunity remains unclear. This review examines mechanisms elucidated in the parent-into-F1 model of lupus and their possible parallels in human lupus pathogenesis.
  
  
  RESULTS
  In the parent-into-F1 model, lupus results from the transfer of normal, foreign reactive CD4 T cells targeted to intrinsically normal F1 B cells. Transfer of normal CD8 T cells prevents lupus, whereas transfer of CD8 T cells with killing defects does not but is correctable with additional in-vivo enhancement of CD8 cytotoxic T lymphocyte (CTL) function. The parent-into-F1 model has two major similarities to Epstein-Barr virus infection: CD4 T-cell-driven polyclonal B-cell hyperactivity and a critical dependence on CD8 CTL for elimination of activated B cells. These similarities are discussed in relation to human lupus pathogenesis.
  
  
  CONCLUSIONS
  Work in the parent-into-F1 model supports the idea that lupus may result from defective CD8 T-cell function and that therapeutic enhancement of CD8 effectors with selective targeting to autoreactive B cells may be beneficial. Despite strong evidence linking Epstein-Barr virus infection with human lupus, the exact nature of this link requires further study.
authors.affiliation: Pathology Department, Uniformed Services University of Health Sciences, Bethesda, Maryland, USA. cvia@usuhs.mil
authors.forename: Charles S
authors.initials: CS
authors.lastname: Via
mesh_terms: D015551:Autoimmunity / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*