Acquired immunodeficiency in murine lymphoproliferative disease: considerations on pathogenesis.
C57BL/6Kh mice were infected with a single i.p. injection of 1 x 10(5) FFU of LP-BM5 MuLV. The development and progress of the virus-induced lymphoproliferative 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 contrast to previous reports, there was a dramatic increase in the frequency of CD4+ cells in spleens among which over 20% expressed V beta 5 TCR, as compared with fewer than 3% in spleens of normal mice. Spleen cells from infected mice retained their in vitro ability to proliferate upon stimulation with IL-2 and anti-CD3, but were unable to respond when stimulated with phorbol ester and either a low dose of IL-2 or calcium ionophore (ionomycin). A similar pattern of in vitro proliferative responses was obtained when normal spleen cells were treated with K252a compound, a known inhibitor of protein kinase C activity. Together with the observations that viral infection impaired down-regulation of the phorbol-induced kinase activity and that the kinase inhibitor only marginally enhanced suppression of virus-infected cells proliferation, this finding suggests that disturbances of protein kinase C activity may underly the pathological effects seen after viral infection. However, since no apparent quantitative and qualitative changes in protein kinase C itself and its translocation were observed, it is more likely that the virus may interfere with either the substrate or product of kinase activity.
Thacore
H R
HR
Department of Microbiology, School of Medicine, State University of New York, Buffalo.
Cunningham
R K
RK
Zhou
P
P
Nakeeb
S
S
Terzian
R
R
Zaleski
M B
MB
D000818:Animals; D000921:Antibody-Producing Cells / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D015759:Ionomycin / Q000494:pharmacology; D008198:Lymph Nodes / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000473:pathology / Q000503:physiopathology*; D011493:Protein Kinase C / Q000378:metabolism; D013154:Spleen / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015759:Ionomycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium