Tonietti G, Rossi G B, Del Gobbo V, Accinni L, Ranucci A, Titti F, Premrov M G, Garaci E
Cancer Res. 1983 Sep;43(9):4355-63.
The levels of serum thymic factor(s) (STF), of Thy-1.2 positivity of splenocytes [as measured by their azathioprine (AZ) sensitivity], and of Thy-1.2-positive "spontaneous" spleen rosette-forming cells (SSRFCs), as well as the presence of infectious virus in the thymus, were assessed as a function of time after virus inoculation in susceptible DBA/2, partially resistant BALB/c, and fully resistant C57BL/6 mice given the polycythemia- or anemia-inducing strain of Friend leukemia virus (FLV-P and FLV-A, respectively). As early as Days 2 to 3, the levels of STF and of AZ sensitivity of splenocytes were profoundly decreased in DBA/2 mice, and, to a lesser extent, in BALB/c mice given FLV-P; however, SSRFCs/spleen were increased in both mouse strains. Conclusive evidence of infectious FLV-P was obtained in the thymuses of DBA/2 mice soon after infection. In mice of the same strains infected with FLV-A, STF levels were similarly decreased, but AZ sensitivity of splenocytes was unaffected, and SSRFCs were decreased. Evidence of early FLV-A infection in the thymus of DBA/2 mice was likewise obtained. In C57BL/6 mice given FLV-A, STF levels, AZ sensitivity of splenocytes, and SSRFC showed changes similar to, but of lower magnitude than, those in BALB/c mice. On the other hand, in C57BL/6 mice given FLV-P, the decrease in STF and AZ sensitivity was almost as pronounced as in susceptible DBA/2 mice in the face of complete absence of infectious virus or viral markers in the thymuses. The observed changes are ascribed to virus infection in view of the following: (a) good temporal correlation between these changes and virus infection; (b) absence of any change in mice given heat-inactivated viruses or spleen homogenate of normal DBA/2 mouse spleen; (c) overall good correlation between mouse genotype and genetic (Fv-1 and Fv-2) restrictions of virus infection on one hand and the magnitude of the observed changes on the other. In particular, the decrease in STF and SSRFC levels is ascribed to the replication-competent (Friend-murine leukemia virus) component of Friend leukemia virus complex, whereas the decrease in AZ sensitivity of splenocytes and the increase of SSRFCs are ascribed to the defective spleen focus-forming virus component of the complex. All changes described so far were transient, since they were not detectable beyond 42 days after virus inoculation in overtly leukemic animals. The observed derangements of thymus-derived immune functions may play an important cofactor role during the onset of leukemia in mice genetically permissive to Friend leukemia virus replication and transformation, but they do not seem relevant to the maintenance of leukemia.
在接种诱导红细胞增多症或贫血症的弗瑞德白血病病毒（分别为FLV-P和FLV-A）后，对易感的DBA/2、部分抗性的BALB/c和完全抗性的C57BL/6小鼠，评估了血清胸腺因子（STF）水平、脾细胞Thy-1.2阳性率[通过其硫唑嘌呤（AZ）敏感性来衡量]、Thy-1.2阳性“自发”脾玫瑰花结形成细胞（SSRFC）水平，以及胸腺中感染性病毒的存在情况，并将其作为病毒接种后时间的函数。早在第2至3天，DBA/2小鼠以及接种FLV-P的BALB/c小鼠中，STF水平和脾细胞的AZ敏感性就大幅下降；然而，两种小鼠品系中SSRFC/脾的数量均增加。感染后不久，就在DBA/2小鼠的胸腺中获得了感染性FLV-P的确切证据。在感染FLV-A的相同品系小鼠中，STF水平同样下降，但脾细胞的AZ敏感性未受影响，且SSRFC数量减少。同样也获得了DBA/2小鼠胸腺中早期FLV-A感染的证据。在接种FLV-A的C57BL/6小鼠中，STF水平、脾细胞的AZ敏感性和SSRFC表现出与BALB/c小鼠相似但程度较低的变化。另一方面，在接种FLV-P的C57BL/6小鼠中，尽管胸腺中完全没有感染性病毒或病毒标志物，但STF和AZ敏感性的下降几乎与易感的DBA/2小鼠一样明显。鉴于以下情况，观察到的这些变化归因于病毒感染：（a）这些变化与病毒感染之间存在良好的时间相关性；（b）接种热灭活病毒或正常DBA/2小鼠脾脏的脾匀浆的小鼠没有任何变化；（c）一方面小鼠基因型与病毒感染的遗传（Fv-1和Fv-2）限制之间，另一方面与观察到的变化程度之间总体具有良好的相关性。特别是，STF和SSRFC水平的下降归因于弗瑞德白血病病毒复合物中有复制能力的（弗瑞德-鼠白血病病毒）成分，而脾细胞AZ敏感性的下降和SSRFC的增加归因于该复合物中有缺陷的脾集落形成病毒成分。到目前为止所描述的所有变化都是短暂的，因为在明显白血病动物中，病毒接种后42天以上就检测不到这些变化了。在对弗瑞德白血病病毒复制和转化具有遗传易感性的小鼠白血病发病过程中，观察到的胸腺来源免疫功能紊乱可能起重要的辅助因子作用，但它们似乎与白血病的维持无关。
