Reactivity in neoplasia, preneoplasia, and pregnancy of lymphocytes against fetal extracts: cross-reactions between man and mouse.

KCl extracts (3 M) from human fetuses were tested by macrophage electrophoretic mobility (MEMB), leukocyte migration inhibition, and/or leukocyte adherence inhibition techniques against lymphocytes-leukocytes from tumor-bearing humans and control persons. A positive MEMB test was found in 209 of 284 (73%) patients with various types of clinically manifest tumors. Only 15 of 134 (11%) controls gave a positive reaction by the MEMB test. Leukocyte migration was significantly inhibited in 48 of 64 (75%) tumor patients, and leukocyte adherence was significantly inhibited in 40 of 50 (80%) tumor patients versus 7 of 50 (14%) and 10 of 54 (19%) in the corresponding controls. Lymphocyte reactivity to fetal extracts is also detectable in inbred XVII/Bln, CBA/Bln, and C3H/Bln mice bearing spontaneous or transplanted tumors of different etiology. Human and mouse fetal extracts gave cross-reactions. Lymphocytes from tumor-bearing mice were reactive against fetal extracts from the cow, pig, sheep, guinea pig, cat, and chicken. Mice bearing benign skin warts induced by 7,12-dimethylbenz[a]anthracene (DMBA) as well as DMBA-treated mice without visible skin lesions gave a positive MEMB test. Likewise, pregnancy is associated with lymphocyte reactivity to fetal extracts.

Lymphocyte reactivity in normal and malignant cell proliferation against a phylogenetically conserved antigen in fetal extracts.

Lymphocyte reactivity to 3-M KCl extracts from fetuses of different species of origin was shown by the macrophage electrophoretic mobility (MEMB) and/or the leukocyte migration inhibition tests in tumor-bearing mice and humans. In chemical carcinogenesis, reactivity was detectable before tumors developed. Six weeks after sc injection of 1,000 micrograms benzo[a]pyrene [(BP) CAS: 50-32-8] into XVII/Bln mice, the MEMB test became positive. The latent period was 15 weeks after 1.0 micrograms BP, indicating a dose-response relationship of the phenomenon. Painting of mouse skin with 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6], croton oil (CAS: 8001-28-3), or benzene (CAS: 71-43-2) had the same sensitizing effect as BP. In contrast to the strong carcinogens BP and DMBA that caused lymphocyte reactivity to persist until tumors developed, benzene and the promoter croton oil induced only a transient effect. Termination of treatment abolished reactivity within 12 weeks. Lymphocyte reactivity to fetal extract in normal cell proliferation was evident from the fact that two-thirds-hepatectomized rats and BCG-treated mice became MEMB-positive. In hepatectomized rats the effect was reversible according to the completion of liver regeneration. Lymphocytes from tumor-bearing mice reacted with mouse and human fetal extract as well as with extracts from different developmental stages of frogs and fish. Fetal extracts were assumed to contain a phylogenetically conserved antigen.

[Influence of BCG on the production of antibody-forming cells in the primary and secondary immune response against sheep erythrocytes in the mouse]. / Einfluss von BCG auf die Produktion Antikörper bildender Zellen in der primären und sekundären Immunantwort gegen Schaferythrozyten bei der Maus

Adult mice react with an increased production of PFC (plaque-forming cells) against sheep erythrocytes (SE). in the primary immune response after application of BCG. Animals receiving 0,5 mg of BCG 10 days before SE show an increase in direct PFC of more than 50%. No effect was observed after injecting BCG 14 or 5 days before SE or using a dose of 0,1 mg of BCG. The results indicate that the effect of BCG on the humoral immune response is influenced by the interval between application of BCG and the SE as well as the BCG-dose. By contrast, BCG had no significant influence on the secondary humoral immune response. In a few cases the immune response seemed to be suppressed.

[The macrophage electrophoresis mobility (MEM) test for detection of cell sensitivity: technical analyses. I. Guinea pig peritoneal cells as indicator cells in the MEM test]. / Der Makrophagen-Elektrophorese-Mobilitäts-(MEM-) Test zum Nachweis zellulärer Sensibilisierungen: Methodische Untersuchungen. I. Peritonealzellen des Meerschweinchens als Indikatorzellen im MEM-Test.

The influence of cell selection and the time of harvesting the indicator cells (peritoneal cells of the guinea pig) on the test result was studied. In order to obtain positive test results, it is not necessary to select the cells. The time of preparation of peritoneal cells following paraffin oil application has no effect on the test result. Peritoneal cells from animals not stimulated with oil also yielded positive MEM test results. 'False negative' results in MEM studies are, to some extent, attributable to the macrophage indicator cell system.

Differences of the in vitro reactivity of lymphocytes from normal and persistently lymphocytotic cows to enzootic bovine leukosis tumour membrane extracts as detected with the macrophage-electrophoretic mobility test.

The response of peripheral blood lymphocytes from normal and persistently lymphocytotic cows to cell membranes and sodium cholate-extracted membrane proteins from normal and tumourous lymph nodes was tested with the macrophage-electrophoretic-mobility test with guinea pig peritoneal macrophages as indicator cells. Lymphocytes from 13 cows with persistent lymphocytosis (PL) showed a positive reaction with cholate extracts from tumour cell membranes. On the other hand, there was a negative reaction with corresponding extracts from normal lymph nodes for 11 animals. 4 of 10 hematologically normal cows also showed a positive reaction against tumour cell membrane extracts. One of these, however, thereafter developed antibodies against BLV glycoprotein gp 51. Using tumour cell membrane preparations as antigen, the 4 cows with PL tested also exhibited a positive reaction, whereas none of 3 hematologically normal cows showed any reactivity. As efforts to detect the main antigenic proteins of BLV (gp 51, p 24) in detergent extracts of tumour cell membranes proved unsuccessful, these findings are thought to provide evidence for the existence of a common non-viral antigen on cell membranes of bovine leukosis tumour cells.

[Lymphocyte reactivity of tumor-bearing mice to a 3M KCl extract of fetal mouse tissue: removal of diffusion chambers containing tumor cells reverses the reactivity]. / Lymphozytenreaktivität tumortragender Mäuse gegen 3M KCl-Extrakte aus Mausfötalgewebe: Die Entfernung von Diffusionskammern mit Tumorzellen hebt die Reaktivität auf.

Sensitization of lymphocytes to 3M KCl fetal extracts was shown by the MEM test after diffusion chambers containing tumor cells have been implanted into mice. Lymphocyte reactivity was still present 2, 4 and 6 weeks after removal of the chambers. When tested after 9 and 12 weeks the sensitization was no longer detectable. This results show the reversibility of sensitization after complete removal of tumor cells.

[Lymphocyte reactivity against fetal antigens during the growth and regression of experimental tumors]. / Lymphozytenreaktivität gegen Fötalantigene während des Wachstums und der Rückbildung experimenteller Tumoren.

Sensitization of lymphocytes occurs to fetal antigens during growth of malignant tumours. Sensitization was measured by the MEM-technique. Antigenic preparations, obtained by extraction with 3 M KCl of mouse fetal tissues were used. Growing tumors after allogenic transplantation of tumour cells gave rise to cellular sensitization. The disappearance of the tumours resulted in a decrease of the sensitization status. Lymphocytic sensitization to fetal antigens was evident in mice with intradermally growing tumors, too. After ligation, followed by regression of the tumours the sensitization became no longer detectable. The results show that tumour regression is associated with reversibility of cellular sensitization to fetal antigens.

[Cross-reactivity of 3M KCl-extracts of fetal tissue from various species in the macrophage electrophoresis mobility test. II. Tissue extracts from lower vertebrates in various phases of development]. / Kreuzreaktivität von 3M KCl-Extrakten aus Fötalgewebe verschiedener Spezies im Makrophagen-Elektrophorese-Mobilitäts- (MEM-) Test. II. Extrakte aus Geweben niederer Wirbeltiere verschiedener Entwicklungsphasen.

Cellular sensitization was detected by the MEM-test using 3M KCl-extracts of fetuses from man and mouse and of different metamorphic stages of the water frog (tadpoles) and the carp (yolk sack-bearing stage). The sensitization demonstrated was independent on the type of tumor tested. The occurrence of active components in the extracts was correlated with certain stages of individual development of water frog and carp. The evidence of these components in species of several classes of vertebrates confirms the assumption of phylogenetically conserved structures.

[Cross-reactivity of 3M KCl extracts of fetal tissue from various species in the macrophage electrophoresis mobility (MEM) test. I. Extracts from fetuses of mammals and one species of fowl]. / Kreuzreaktivität von 3M KCl-Extrakten aus Fötalgewebe verschiedener Spezies im Makrophagen-Elektrophorese-Mobilitäts-(MEM-) Test.

Extracts were prepared by the 3M KCl method from fetal tissues of human, mouse, cattle, pig, sheep, cat, guinea pig, and chicken origin. Lymphocytes of tumor bearing mice and tumor patients reacted specifically in the MEM-test with antigenic components of the extracts. The cellular sensitization of the tumor-bearer was not correlated with the localization and the histologic type of the tumor. The cross-reacting oncofetal antigens obviously represent phylogenetically conserved structures.

[Cellular sensitization to fetal antigens during chemical carcinogenesis]. / Zelluläre Sensibilisierung gegen Fötalantigene während der chemischen Kanzerogenese.

Tumor-bearing mice show a cellular sensitization to fetal antigens as detected by the macrophage electrophoretic mobility (MEM) test. Sensitization is independent of etiological and histological tumor factors. An identical state of sensitization can be found after application of chemical carcinogens (N-methyl-N-nitrosourea, benz(a)pyrene or 7,12-dimethylbenz(a)anthracene) before the tumors have developed. The results indicate that the effect is dose-dependent.

[Detection of cellular sensitization in mice after treatment with chemical carcinogens]. / Der Nachweis zellulärer Sensibilisierungen bei Mäusen nach der Behandlung mit chemischen Kanzerogenen.

Mice were treated epicutaneously (DMBA, benzene) and subcutaneously (BP, MNH) with chemical carcinogens. As detected by the MEM-test a cellular sensitization developed against fetal antigens, which are present in 3M KCl-extracts of mouse fetal tissue. The sensitization was detected before formation of tumors occurred. The conclusion was drawn that sensitization to fetal antigens is not a characteristic feature of tumor-bearing animals.

Cellular sensitization in man and mice during pregnancy to fetal antigens as detected by lympholine assays.

Soluble extracts were prepared by the 3 M KC1 method from human mouse fetuses at different stages of development. As shown by macrophage electrophoretic mobility and by leukocyte migration inhibition tests a high percentage of pregnant women is sensitized to components of these extracts. The testing of pregnant mice of an inbred strain gave similar results. The available data support the view that some kind of cellular sensitization to fetal antigen may occur during pregnancy.