I. Prevention of spontaneous AKR T cell lymphomagenesis by 24-666, a virus isolated from an AKR B cell lymphoma

Abstract

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 Thyl.1 level and in the CD4+CD8+ population and an increase in CD4 −CD8 − cells and in μ + 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.