The maedi-visna virus Tat protein induces multiorgan lymphoid hyperplasia in transgenic mice.

Sheep infected with maedi-visna virus experience immunological disorders leading to progressive chronic diseases involving the brain, lung, spleen, and lymph nodes. To study the biological activity of the viral transactivating Tat protein, we generated transgenic mice carrying the tat gene. Analysis of the transgenic mouse tissues for tat mRNA revealed that while low at the messenger level, the expression of the transgene correlated with dramatic follicular lymphoproliferative disorders involving the lung, spleen, lymph nodes, and skin. This finding suggests that the viral protein possesses a high pathological potency. Our findings show that the maedi-visna virus tat gene product contributes to the pathogenesis of multiorgan proliferative disorders associated with maedi-visna virus infection.

c-fms expression in acute leukemias with complex phenotypes.

The c-fms proto-oncogene product, which is the receptor for the macrophage colony-stimulating factor CSF-1, is always found expressed in acute myeloid leukemia cells, irrespective of their stage of differentiation according to the FAB classification (Dubreuil P, Torrès H, Courcoul M, Birg F, Mannoni P. Blood 1988;72:1081-1085). We have extended this study and looked for c-fms expression in poorly differentiated myeloid leukemias, in a series of acute leukemias of either T or B origin and in biphenotypic leukemias. We now report that expression of c-fms is still related to the myeloid origin of the leukemic proliferation, but that it can also be found in some acute leukemias presenting clonal rearrangements of the T cell receptor gene. Thus expression of the c-fms/CSF-1 receptor may not be exclusively a marker for myeloid proliferations.

c-fms expression is a molecular marker of human acute myeloid leukemias.

The c-fms protooncogene product was identified as the CSF-1 or M-CSF receptor, a polypeptide growth factor that plays a major role in myelomonocytic differentiation. This led us to look for expression of c-fms in fresh acute myeloid leukemia (AML) cells, using Northern blot analysis. c-fms expression was found in the leukemic cells of 28 AML patients, regardless of their stage of differentiation, which was assessed in the French-American-British (FAB) classification. However, the level of c-fms expression was especially high in AML of the M5 stage. High levels of expression were not accompanied by either amplification or rearrangements of the c-fms gene in AML cell DNAs. In contrast, c-fms expression was not found in acute lymphoid leukemias, whether of T or B origin. Thus, c-fms expression appears as a specific molecular marker of leukemogenesis in the myeloid lineage.

Major H-2 and non-H-2 differences between parental strains prevent occurrence of fetectomy-induced yolk sac teratomas.

We performed fetectomies, according to the technique of Sobis and Vandeputte for the surgical induction of teratomas, in female mice mated with syngeneic, congeneic, or allogeneic males. Benign teratomas including multiple tissue formations derived from the three germinal layers were observed only in syngeneic pregnancies. In addition, the frequency of induced teratomas was lower in some strains (A/Sn, A . By, and A . SW) than in others (A . CA, B10 . A, C57BL/6, and C3H/He). This variable frequency may be explained by postulating the existence of fetal, strain-specific antigens. In hybrid pregnancies we observed no complete teratomas, but only cartilaginous formations considered as vestiges of early teratoma differentiation. The maternal immune reaction against either major (H-2) or minor (non-H-2) paternal histocompatibility antigens was sufficient to suppress the development of teratomas from visceral yolk sac of hybrid fetuses. This reaction, including both a serological and a cell-mediated activity, was measured in vitro. These results suggest that a maternal immune reaction is not efficiently altered by the normal first half of pregnancy and that differentiated teratoma tissues express the paternal antigens sufficiently to induce their immune rejection.