Transgenic expression of Fas in T cells blocks lymphoproliferation but not autoimmune disease in MRL-lpr mice.
Fas is a member of the TNF receptor family. Binding of Fas ligand to Fas induces apoptosis in Fas-bearing cells. Fas is expressed in various cells, including thymocytes, peripheral T cells, and activated B cells. The mouse lpr mutation is a loss of function mutation of Fas. MRL-lpr/lpr mice develop lymphadenopathy and splenomegaly, and produce multiple autoantibodies, which results in autoimmune disease. In this report, we describe the establishment of a line of Fas transgenic MRL-lpr mice in which mouse Fas cDNA was expressed using the T cell-specific murine lck promoter. The transgenic mice expressed functional Fas in thymocytes and peripheral T cells, but not in B cells. The transgenic mice did not accumulate abnormal T cells (Thy-1+ B220+), but still accumulated B cells (Thy-1- B220+); they produced a large quantity of Igs (IgG1 and IgG2a), including anti-DNA Abs, and developed glomerulonephritis. These results suggest that autoreactive or activated B cells must be killed through Fas expressed in the B cells by the Fas ligand expressed in activated T cells.
Fukuyama
H
H
Department of Genetics, Osaka University Medical School, Suita, Japan.
Adachi
M
M
Suematsu
S
S
Miwa
K
K
Suda
T
T
Yoshida
N
N
Nagata
S
S
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015870:Gene Expression; D007074:Immunoglobulin G / Q000097:blood; D008206:Lymphatic Diseases / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics*
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D019014:fas Receptor