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 NK cells is not affected by the scid mutation. Mouse NK 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 GM anti-serum (alpha-asialo GM1), for in vivo depletion of endogenous NK cell function, develop lethal Epstein-Barr virus (EBV)-induced lymphoproliferative disorders (EBV-LPD) at lower doses od inoculated EBV-transformed lymphoblastoid 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 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 NK-sensitive cell line YAC-1 and human EBV-LCL than splenocytes obtained from untreated SCID mice.
Lacerda
J F
JF
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Ladanyi
M
M
Jagiello
C
C
O'Reilly
R J
RJ
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D001402:B-Lymphocytes / Q000276:immunology / Q000637:transplantation / Q000821:virology; D002472:Cell Transformation, Viral; D003602:Cytotoxicity, Immunologic; D005677:G(M1) Ganglioside / Q000037:antagonists & inhibitors* / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D011817:Rabbits; D013154:Spleen / Q000276:immunology; D014183:Transplantation, Heterologous
D000906:Antibodies; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside