Growth and dissemination of human malignant lymphoblasts in immunosuppressed nu/nu mice.
Athymic nu/nu mice are commonly employed for the heterotransplantation of solid human tumors. Leukemias, however, have consistently proved difficult to transplant and, to enhance their take, recipient nu/nu mice have been variously immunosuppressed. In this study, the natural reactivity against human malignant T lymphoblast (PF382) of splenectomized nu/nu mice (S-nu/nu), nu/nu mice splenectomized and treated with polyinosinic-polycytidylic acid (SIC-nu/nu), and nu/nu mice splenectomized, irradiated and repeatedly injected with antiasialo GM1 antiserum (SIA-nu/nu) has been correlated with the in vivo growth of subcutaneous and intravenous PF382 cell challenges. SIC-nu/nu mice display a marked natural killer (NK) activity, quickly clear 125I-Urd-labelled PF382 cells injected intravenously and do not allow the growth of subcutaneous nor intravenous PF382 cell challenges. S-nu/nu mice display a slightly lower NK activity and slower clearance of 125I-Urd-labelled PF382 cells. Moreover, an intravenous PF382 cell challenge kills 56% of S-nu/nu mice. SIA-nu/nu mice have no NK activity, slowly clear 125I-Urd-labelled PF382 cells and always allow the growth of PF382 cells injected either subcutaneously or intravenously with a consistent pattern. Following the intravenous challenge, PF382 cells first metastasize to liver and kideny, then focal or diffuse infiltrations of the bone marrow and menings become evident. SIA-nu/nu mice thus offer an interesting experimental model for study of the pathogenesis of leukemic infiltration of the meninges, and the exploration of possible therapeutic approaches.
Cavallo
F
F
Institute of Microbiology, University of Turin, Italy.
Riccardi
C
C
Forni
M
M
Pericle
F
F
Bosco
M C
MC
Giovarelli
M
M
Soleti
A
A
Forni
G
G
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D005677:G(M1) Ganglioside / Q000008:administration & dosage; D006801:Humans; D007165:Immunosuppression Therapy; D007275:Injections, Intravenous; D007680:Kidney Neoplasms / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000276:immunology* / Q000473:pathology; D011070:Poly I-C / Q000008:administration & dosage; D014183:Transplantation, Heterologous / Q000379:methods; D014407:Tumor Cells, Cultured
D005677:G(M1) Ganglioside; D011070:Poly I-C