Administration of rabbit anti-asialo GM1 antiserum facilitates the development of human Epstein-Barr virus-induced lymphoproliferations in xenografted C.B-17 scid/scid mice

Mice with severe combined immune deficiency (C.B-17 scid/scid [SCID mice]) lack functional B and T lymphocytes and are permissive for the growth of human xenografts. However, the development of functional Nh cells is not affected by the scid mutation. Mouse Nh cells express the surface glycolipid asialo GM1 and are implicated in the rejection of heterotransplanted cells. In the present study, we demonstrate that SCID mice treated with rabbit anti-asialo GM1 antiserum (cu-asialo GM1), for in vivo depletion of endogenous Nh cell function, develop lethal Epstein-Barr virus (EBV)-induced lymphoproliferative disorders (EBV-LPD) at lower doses of inoculated EBV-transformed lym-phoblastoid B cell lines (EBV-LCL) than untreated animals. Furthermore, at any given dose of EBV-LCL inoculated, EBV-LPD developed earlier and induced lethality sooner in alpha-asialo GM1-treated animals. We also demonstrate that SCID mice treated with alpha-asialo GM1 have a reduction in the number of asialo GM1-expressing splenocytes. Moreover, splenic cell suspensions derived from alpha-asialo GM1-treated SCID mice show lower cytotoxicity against the mouse MK-sensitive cell line YAC-1 and human EBV-LCL than splenocytes obtained from untreated SCID mice.