Prevention of spontaneous AKR T cell lymphomagenesis by 24-666, a virus isolated from an AKR B cell lymphoma.
Injection of a nonlymphomagenic ecotropic virus 24-666 isolated from a B cell lymphoma of AKR origin into young AKR mice (1-60 days old) inhibited spontaneous T cell lymphoma development. The reduction in T cell lymphoma incidence (16/106-15%) was accompanied with the appearance of B cell lymphomas (16/106-34%) in older mice (500 days mean latency). Infection of newborn to 60-day-old AKR mice with 24-666 prevented changes in thymus subpopulations and expression of MuLV-related cell surface antigens, normally observed in the thymus of 5- to 6-month-old AKR mice prior to lymphoma development. Thymuses of 24-666-infected 9- to 12-month-old mice lacked recombinant dual tropic virus (DTV) expression and retained the thymus pattern of 2-month-old AKR mice. At 12 months after 24-666 administration a striking decrease in Thy1.1 level and in the CD4+ CD8+ population and an increase in CD4- CD8- cells and in mu+ B cells, predominantly Ly1+, were observed. The presence of B cells in these thymuses was also reflected in the high response of thymocytes to LPS blastogenesis accompanied by a decreased response to PHA. Although T cell lymphoma development was markedly reduced by 24-666 administration, the establishment of potential lymphoma cells (PLC) was not affected. Transfer of lymphoid cells from 12-month-old grossly normal 24-666-infected mice to the appropriate recipients resulted in a high incidence (64-80%) of B cell lymphoma development. Thus, 24-666 seems to act through interference with the establishment of DTV in the thymus, thereby preventing PLC promotion to overt T cell lymphomas. Lack of the favorable microenvironment for PLC development in the T cell pathway enables PLC development in the B cell pathway in older mice.
Peled
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A
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Haran-Ghera
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N
D000375:Aging; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens; D015994:Incidence; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000382:microbiology*; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008806:Mice, Inbred AKR; D009858:Oncogenic Viruses / Q000276:immunology*; D018800:Thy-1 Antigens
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D015704:CD4 Antigens; D016827:CD8 Antigens; D018800:Thy-1 Antigens