Chronic immune stimulation is required for Moloney leukaemia virus-induced lymphomas

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Abstract
C-type viruses are known to be aetiologically related to naturally occurring leukaemia in a variety of species1, although the mechanisms of transformation are largely unknown. The long latency periods, requirement for an acute viraemia and monoclonality of the tumours2,3 distinguish leukaemogenesis from neoplasias induced by the acute transforming viruses and suggest an indirect mechanism. Consistent with this is the lack of in vitro transforming activity of replication-competent leuk-aemogenic viruses4. We have shown previously that the presence of T cells which proliferate in vitro in response to viral antigens is uniquely associated with the conditions leading to leukaemia. Based on these observations we have hypothesized that chronic immune stimulation is required for leukaemogenesis. We now demonstrate that CBA/N mice, when inoculated as newborns with Moloney leukaemia virus (MoLV), develop an acute viraemia but do not develop leukaemia or have detectable T-cell responses against the virus. This supports the hypothesis that chronic immune stimulation is essential for leukaemogenesis.