Ectopic Expression of B7-1 (CD80) on T Lymphocytes in AutoimmunelprandgldMice

Defective Fas-mediated apoptosis in mice, caused by thegldmutation in thefas ligandgene, results in the development of lupus-like autoantibodies and severe lymphoproliferation. We previously demonstrated ectopic expression of the costimulatory molecule B7-1 (CD80) on T lymphocytes in B6/gldmice. This report extends these observations by demonstrating similar results in B6/lprmice, which possess a mutation in the gene encoding Fas. Additionally, we demonstrate that this phenomenon is age-dependent and occurs on multiple subsets of B6/gldT lymphocytes. B7-1 upregulation is observed on T cells from both conventionally housed and specific-pathogen-free B6/gldmice, suggesting that this is not a consequence of infection by pathogen. T cells fromlprandgldmice show increased binding of CTLA4-Ig fusion protein, suggesting that the upregulated B7-1 is functional. CD28, a receptor for B7-1 which activates T cells, is upregulated in B6/lprand B6/gldmice, while CTLA4, a negative regulator of T cells which binds B7-1, is not. Our results suggest that ectopic expression of B7-1 on T cells oflprandgldmice may be playing a role in exacerbation of lymphoproliferation and/or autoimmunity.