EFFECT OF NON-H-2-LINKED GENES ON ANTI-VIRUS IMMUNE-RESPONSES AND LONG-TERM SURVIVAL IN MICE PERSISTENTLY INFECTED WITH E-55-VIRUS( MURINE LEUKEMIA)

We have previously demonstrated that BALB/c-H-2(k) (BALB.K) mice are s usceptible to the development of thymic lymphoma induced by E-55+ muri ne leukemia virus (MuLV). In the present studies, C57BL/10-H-2(k) (B10 .BR) mice were found to be resistant to E-55+ MuLV-induced lymphoma de spite the fact that these mice become persistently infected. This resi stance to lymphomagensis is mediated by the anti-virus immune response since immunosuppressed mice progress to develop disease. The protecti ve immune response in B10.BR mice is bimodal with respect to time afte r virus infection. The early immune response results in a dramatic dec rease in the number of virus-infected cells within 4-8 weeks after inf ection. This decrease in virus-infected cells occurs in immunocompeten t mice from strains that are either resistant (B10.BR) or susceptible (BALB.K) to E-55+ MuLV-induced disease. Subsequently, susceptible mice develop an increase in infected cells, whereas no increase in infecte d cells occurs in resistant mice despite the fact that they are persis tently infected. This later phase of resistance in B10.BR appears to b e mediated by T cells. Since B10.BR and BALB.K both express the H-2(k) haplotype, resistance appears to be mediated by a non-H-2-linked gene (s). (BALB.K x B10.BR)F-1 mice are resistant to disease development, i ndicating resistance is a dominant trait. (C) 1995 Academic Press, Inc .