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 re trovirus-induced murine acquired immunodeficiency syndrome (MAIDS) cau sed by LP-BM5 murine leukemia virus (MuLV) mixtures increased the expr ession of Fas antigen (Fas) during progression of the disease. However , the contribution of the Fas/Fas ligand (Fas L) system to the pathoge nesis 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(-) CD4 T cells and Ig kappa dull B220(+) cells, which are characteristic of MA IDS, increased after the inoculation of LP-BM5 MuLV in B6 Ipr/lpr mice . B220(+) TCR alpha beta T cells, unique to lupus prone mice, also inc reased in the B6 lpr/lpr mice after infection. CD4(+) B220(+) TCR alph a 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(+) TC R alpha beta T cells observed in non-infected B6 lpr/lpr mice were lar gely of the CD4(-)CD8(-) phenotype. A DNA PCR analysis of the LP-BM5 M uLV-infected B6 lpr/lpr mice revealed the genome integration of defect ive 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, whi le MAIDS-infected B6 +/+ mice usually died within 5 to 6 months, and B 6 lpr/lpr mice not infected with LP-BM5 MuLV lived more than 6 months. Taken together, these results suggest that MAIDS is inducible indepen dently with functional Fas expression and the possibility of accelerat ed progression of murine AIDS and lpr-associated autoimmune disease in B6 lpr/lpr mice infected with LP-BM5 MuLV.