Purpose of review: 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.
Recent findings: 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.
Summary: 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.