Accelerated progression of a murine retrovirus-induced immunodeficiency syndrome in Fas mutant C57BL/6 lpr/lpr mice.
We reported previously that CD4+ T cells and B cells in mice with retrovirus-induced murine acquired immunodeficiency syndrome (MAIDS) caused by LP-BM5 murine leukemia virus (MuLV) mixtures increased the expression of Fas antigen (Fas) during progression of the disease. However, the contribution of the Fas/Fas ligand (Fas L) system to the pathogenesis of MAIDS remained unknown. Here, we examined the susceptibility of C57BL/6 (B6) lpr/lpr mice, which has been reported to be defective for the expression of Fas, to MAIDS. We found that the Thy1.2- CD4T cells and Ig kappa dull B220+ cells, which are characteristic of MAIDS, increased after the inoculation of LP-BM5 MuLV in B6 lpr/lpr mice. B220+ TCR alpha beta T cells, unique to lupus prone mice, also increased in the B6 lpr/lpr mice after infection. CD4+ B220+ TCR alpha beta T cells increased profoundly among the B220+ TCR alpha beta T cells from LP-BM5 MuLV-infected B6 lpr/lpr mice, while the B220+ TCR alpha beta T cells observed in non-infected B6 lpr/lpr mice were largely of the CD4-CD8- phenotype. A DNA PCR analysis of the LP-BM5 MuLV-infected B6 lpr/lpr mice revealed the genome integration of defective LP-BM5 virus, further confirming that MAIDS is inducible to B6 lpr/lpr mice. LP-BM5 MuLV-infected lpr/lpr mice died within 3 months, while MAIDS-infected B6 +/+ mice usually died within 5 to 6 months, and B6 lpr/lpr mice not infected with LP-BM5 MuLV lived more than 6 months. Taken together, these results suggest that MAIDS is inducible independently with functional Fas expression and the possibility of accelerated progression of murine AIDS and lpr-associated autoimmune disease in B6 lpr/lpr mice infected with LP-BM5 MuLV.
Hiromatsu
K
K
Laboratory of Host Defense, Nagoya University School of Medicine, Aichi, Japan.
Usami
J
J
Aoki
Y
Y
Makino
M
M
Yoshikai
Y
Y
D000818:Animals; D017209:Apoptosis; D003673:Defective Viruses / Q000302:isolation & purification; D018450:Disease Progression; D009052:Leukemia Virus, Murine / Q000302:isolation & purification; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008817:Mice, Mutant Strains; D016183:Murine Acquired Immunodeficiency Syndrome / Q000209:etiology* / Q000276:immunology / Q000401:mortality; D010641:Phenotype; D012367:RNA, Viral / Q000302:isolation & purification; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019014:fas Receptor / Q000235:genetics*
D012367:RNA, Viral; D019014:fas Receptor