ACQUIRED IMMUNODEFICIENCY IN MURINE LYMPHOPROLIFERATIVE DISEASE - CONSIDERATIONS ON PATHOGENESIS

C57BL/6Kh mice were infected with a single i.p. injection of 1x10(5) F FU of LP-BM5 MuLV. The development and progress of the virus-induced l ymphoproliferative disease was followed for 12 weeks after infection. As anticipated, progressive splenomegaly and lymphadenopathy, as well as almost total abrogation of immune responsiveness ensued. In contras t to previous reports, there was a dramatic increase in the frequency of CD4(+) cells in spleens among which over 20 % expressed V-beta 5 TC R, as compared with fewer than 3 % in spleens of normal mice. Spleen c ells from infected mice retained their in vitro ability to proliferate upon stimulation with IL-2 and anti-CD3, but were unable to respond w hen stimulated with phorbol eater and either a low dose of IL-2 or cal cium ionophore (ionomycin). A similar pattern of in vitro proliferativ e responses was obtained when normal spleen cells were treated with K2 52a compound, a known inhibitor of protein kinase C activity. Together with the observations that viral infection impaired down-regulation o f the phorbol-induced kinase activity and that the kinase inhibitor on ly marginally enhanced suppression of virus-infected cells proliferati on, this finding suggests that disturbances of protein kinase C activi ty may underly the pathological effects seen after viral infection. Ho wever, since no apparent quantitative and qualitative changes in prote in kinase C itself and its translocation were observed, it is more lik ely that the virus may interfere with either the substrate or product of kinase activity,