Expression of mouse mammary tumor virus superantigen accelerates tumorigenicity of myeloma cells.
To investigate whether superantigen (SAG) from endogenous mouse mammary tumor virus functions as an immunogenic or a tumorigenic factor in tumor development, the BALB/c myeloma cell line FO was transfected with the SAG gene from the 3' Mtv-50 long terminal repeat (LTR) open reading frame (ORF), the product of which was specific for Vbeta6. All five transfectants expressing Mtv-50 LTR ORF mRNA showed stimulatory activity for Vbeta6 T-cell hybridomas in vitro; this activity was inhibited by the addition of anti-Mtv-7 monoclonal antibody (MAb) or anti-major histocompatibility complex class II I-A(d) and I-E(d) MAb. All transfectants with the SAG gene grew more rapidly than did mock transfectants in BALB/c mice after subcutaneous inoculation, whereas all clones, including mock transfectants, grew equally well in athymic nude mice. A significant fraction of Vbeta6 T cells selectively expressed activation markers, including CD44(high), CD62L(low), and CD69(high), and produced large amounts of interleukin 5 (IL-5) and IL-6 in BALB/c mice inoculated with transfectants. These results suggested that the expression of viral SAG enhances the tumorigenicity of a myeloma cell line through the stimulation of SAG-reactive T cells.
Umemura
M
M
Laboratory of Host Defense, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466-8550, Japan.
Wajjwalku
W
W
Upragarin
N
N
Liu
T
T
Nishimura
H
H
Matsuguchi
T
T
Nishiyama
Y
Y
Wilson
G M
GM
Yoshikai
Y
Y
D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D018791:CD4 Lymphocyte Count; D005434:Flow Cytometry; D015848:Interleukin-5 / Q000096:biosynthesis / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D007951:Leukemia, Myeloid; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018089:Superantigens / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020079:Terminal Repeat Sequences; D014162:Transfection; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D015848:Interleukin-5; D015850:Interleukin-6; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens