Engraftment and tumorigenesis of HTLV-1 transformed T cell lines in SCID/bg and NOD/SCID mice.
Human T cell leukemia/lymphoma virus type-1 (HTLV-1) is recognized as the etiological agent of adult T cell leukemia (ATL). Although HTLV-1 can immortalize human lymphocytes in culture, identification of molecular events leading to tumorigenesis after HTLV-1 infection remain elusive. SCID/bg and NOD/SCID mice have reduced natural killer (NK) cell activity and were inoculated intraperitoneally with HTLV-1 transformed cells to refine and characterize the SCID mouse as a small animal model for investigation of HTLV-1 tumorigenesis. HTLV-1 transformed cell lines originally derived by cocultivation of uninfected peripheral blood mononuclear cells (PBMC) with lethally irradiated leukemic cells from patient samples (SLB-1, MT-2 and HT-1-RV) were lymphomagenic when inoculated into NOD/SCID mice. In contrast, immortalized cell lines generated by transfection PBMC with an infectious molecular clone of HTLV-1 (ACH or ACH.p12) were not tumorigenic. The differing behaviors of HTLV-1 infected cell lines in NOD/SCID mice indicates that viral infection and immortalization of human PBMC for growth in culture is not sufficient for induction of a tumorigenic phenotype. The higher level of engraftment of HTLV-1 transformed cell lines in NOD/SCID mice suggests that this is an effective animal model to investigate molecular determinants of HTLV-1 lymphomagenesis.
Liu
Yingxian
Y
Department of Microbiology and Immunology, SUNY Upstate Medical University, 750 East Adams St., Syracuse, NY 13210, USA.
Dole
Kiran
K
Stanley
James R L
JR
Richard
Virgile
V
Rosol
Thomas J
TJ
Ratner
Lee
L
Lairmore
Michael
M
Feuer
Gerold
G
D000818:Animals; D002461:Cell Line, Transformed / Q000473:pathology / Q000637:transplantation* / Q000821:virology; D006085:Graft Survival; D015490:HTLV-I Infections / Q000150:complications / Q000473:pathology; D015368:Human T-lymphotropic virus 1; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000821:virology; D008223:Lymphoma / Q000209:etiology / Q000473:pathology / Q000821:virology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D009368:Neoplasm Transplantation / Q000473:pathology; D009374:Neoplasms, Experimental / Q000209:etiology / Q000473:pathology / Q000821:virology