Thacore H R, Cunningham R K, Zhou P, Nakeeb S, Terzian R, Zaleski M B
Department of Microbiology, School of Medicine, State University of New York, Buffalo.
Immunobiology. 1994 Apr;190(3):195-211. doi: 10.1016/S0171-2985(11)80269-X.
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.
C57BL/6Kh小鼠经腹腔注射1×10⁵ FFU的LP - BM5 MuLV进行单次感染。感染后持续观察病毒诱导的淋巴细胞增生性疾病的发展和进程，为期12周。正如预期的那样，随后出现了脾脏进行性肿大和淋巴结病，以及免疫反应几乎完全丧失。与之前的报道相反，脾脏中CD4⁺细胞的频率显著增加，其中超过20%表达Vβ5 TCR，而正常小鼠脾脏中的这一比例不到3%。感染小鼠的脾细胞在受到IL - 2和抗CD3刺激后仍保留其体外增殖能力，但在用佛波酯和低剂量IL - 2或钙离子载体（离子霉素）刺激时无反应。当用已知的蛋白激酶C活性抑制剂K252a化合物处理正常脾细胞时，也获得了类似的体外增殖反应模式。结合病毒感染损害佛波酯诱导的激酶活性下调以及激酶抑制剂仅略微增强对病毒感染细胞增殖的抑制这一观察结果，这一发现表明蛋白激酶C活性的紊乱可能是病毒感染后所见病理效应的基础。然而，由于未观察到蛋白激酶C本身及其转位有明显的定量和定性变化，病毒更有可能干扰激酶活性的底物或产物。
