Immunology of the Mouse Mammary Tumor Virus (MTV): Neutralization of MTV by Mouse Antiserum1

[CANCER RESEARCH 28, US-ItÂ», January 1968]

Brief Communication Immunology of the Mouse Mammary Tumor Virus (MTV): Neutralization of MTV by Mouse Antiserum1

Phyllis B. Blair Department oj Bacteriology and Immunology, and the Cancer Research Genetics Laboratory, University of California, Berkeley, California 94720

The antigenicity of the mouse mammary tumor virus (MTV) quantities were injected intraperitoneally into each test mouse. in species other than the mouse has been recognized for many- Each mouse thus received the amount of MTV contained in years; antisera from rabbits, rats, and guinea pigs immunized 0.01 gm (wet weight) of mammary tissue. The test mice were with MTV-containing tissue extracts are capable of neutralizing 4-week-old BALB/c females. the biologic activity of the virus (1, 2, 3, 6, 9). More recently, The efficacy of the neutralization was measured by the nod- it has been demonstrated that MTV is also immunogenic in uligenic assay for MTV (10), which involves hormonal stimula the mouse; antisera from immunized mice react with MTV tion of hyperplastic alveolar nodule development in the mam antigen in immunodiffusion to produce a precipitate line specific mary glands of mice injected with MTV. Beginning at 8 weeks for MTV (5, 11). The present communication reports that of age, the test mice received daily injections for 13 weeks of mouse antiserum is also capable of neutralizing the biologic l Â¡igestradici 17/3 plus 500 mg deoxycorticosterone acetate. activity of MTV. Five weeks after the last injection, the mice were killed and MTV antigen for immunization of the mice was prepared by their mammary glands were removed and stained in whole centrifugation of MTV in a sucrose density gradient, as pre mount preparations (6). The glands were then examined for viously described (7, 8). The source of virus was milk obtained the presence of hyperplastic nodules as indication of the bio from BALB/cCrgl mice that had been fostered on DBA/2Crgl logic activity of the injected MTV. mice, and therefore were infected with the MTV carried by MTV was neutralized by treatment with the antiserum that strain. Each of five I"/BiCrgl adult female mice received an intra- obtained from immunized mice (Table 1). None of the 10 females injected with MTV combined with this antiserum de peritoneal injection of saline containing the MTV derived from 0.01 ml milk on Days 1, 4, 8, and 22. The mice were bled veloped nodules during the hormonal stimulation, whereas 2 weeks after the last injection, and their sera were pooled and nodules did develop in 7 of 10 females injected with MTV in frozen in a commercial refrigerator. The pooled serum contained saline alone and in 7 of 9 females injected with MTV combined antibodies against MTV, as measured by the development of with normal mouse serum. the precipitate line specific for MTV, when it was tested in Attempts to detect specific immunologie responsiveness in the immunodiffusion against MTV antigen (5). mouse against MTV were unsuccessful until recently (4). The Normal mouse serum for control purposes was obtained from present demonstration that mouse antibodies can neutralize normal adult BALB/c male mice. Serum from several donors the biologic activity of MTV seems to establish firmly that the was pooled and frozen until needed. mouse is, indeed, capable of developing a specific immune re Biologically active MTV for the neutralization experiment sponse against this virus. The immunogenicity of this virus can was prepared from an extract of BALB/cfC3HCrgl lactating now be detected in animals of its natural host species by the mammary gland tissue by sedimentation in the ultracentrifuge, resistance of immunized mice against transplants of MTV- as previously described (3). The neutralization procedure was carried out in vitro at room Table 1 temperature (3, 6). Equal amounts of undiluted mouse serum no. and saline, or saline alone, were combined in test tubes with BALB/c mice injected of nodules the virus preparation so that 1 ml of solution contained MTV i.p. with MTV of of mice per nodule- from 0.05 gm of lactating gland tissue. After 2 hours, 0.2-ml inSalineNormalsuspended mice10910No.with nodules770Averagebearingmouse5.97.1

l Supported by Research Grants E-344 and PRA-37 from the serumImmunemouse American Cancer Society, Inc.; by USPHS Grant CA-05388 from mouse serumNo. the National Cancer Institute ; and by Cancer Research Funds of Development of hyperplastic alveolar nodules in mice given in the University of California. jections of biologically active MTV suspended in saline or in Received August 17, 1967; accepted September 21,1967. mouse serum.

148 CANCER RESEARCH VOL. 28

infected mammary tissue (12), and also by the presence in the Virus with the Agent Found in C3Hf/Crgl Mice. J. Nati. sera of immunized animals of specific antibodies capable both Cancer Inst., 36: 423-429, 1966. of precipitating the virus in immunodiffusion systems and of 7. Blair, P. B., Weiss, D. W., and Pitelka, D. R. Immunology of the Mouse Mammary Tumor Virus: Correlation of the Im neutralizing its biologic activity. munodiffusion Precipitate Line with Type-B Virus Particles. J. Nati. Cancer Inst, 37: 261-277, 1966. REFERENCES 8. Duesberg, P. H, and Blair, P. B. Isolation of the Nucleic Acid of Mouse Mammary Tumor Virus (MTV). Proc. Nati. Acad. 1. Andervont, H. B., and Bryan, W. R. Properties of the Mouse Sei. U. S., 56: 1490-1497, 1966. Mammary-Tumor Agent. J. Nati. Cancer Inst., 6: 143-149, 9. Green, R. G, Moosey, M. M, and Bittner, J. J. Antigenic 1944. Character of the Cancer Milk Agent in Mice. Proc. Soc. 2. Bittner, J. J., and Imagawa, D. T. Effect of the Source of the Exptl. Biol. Med., 61: 115-117, 1946. Mouse Mammary Tumor Agent (MTA) upon Neutralization 10. Nandi, S. New Method for Detection of Mouse Mammary of the Agent with Antisera. Cancer Res., 15: 464-468, 1955. Tumor Virus. II. Effect of Administration of Lactating Mam 3. Blair, P. B. Serologie Comparison of Mammary Tumor Viruses mary Tissue Extracts on Incidence of Hyperplastic Mammary from 3 Strains of Mice. Proc. Soc. Exptl. Biol. Med., 103: Nodules in BALB/cCrgl Mice. J. Nati. Cancer Inst, 31: 75- 188-190, 1960. 89, 1963. 4. Blair, P. B. Immunology of the Murine Mammary-Tumor 11. Nowinski, R. C, Old, L. J, Moore, D. H, Geering, G, and Virus (MTV) : Development of Methods of Assay. In: W. J. Boyse, E. A. A Soluble Antigen of the Mammary Tumor Burdette, (ed.), Viruses Inducing Cancer, pp. 288-301. Salt Virus. Virology, 31: 1-14, 1967. Lake City: University of Utah Press, 1966. 12. Weiss, D. W, Lavrin, D. H, Dezfulian, M, Vaa&d, J, and 5. Blair, P. B., Lavrin, D. H., Dezfulian, M., and Weiss, D. W. Blair, P. B. Studies on the Immunology of Spontaneous Mam Immunology of the Mouse Mammary Tumor Virus (MTV) : mary Carcinomas of mice. In: (a) W. J. Burdette (ed.), Identification in Vitro of Mouse Antibodies against MTV. Viruses Inducing Cancer, pp. 138-168. Salt Lake City: Uni Cancer Res., 26: 647-651, 1966. versity of Utah Press, 1966; and (b) R. J. C. Harris (ed.), 6. Blair, P. B., and Weiss, D. W. Immunology of the Mouse Specific Tumour Antigens, pp. 210-230. Copenhagen: Munks- Mammary Tumor Virus: Comparison of Mammary Tumor gaard, 1967.

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Downloaded from cancerres.aacrjournals.org on September 29, 2021. © 1968 American Association for Cancer Research. Immunology of the Mouse Mammary Tumor Virus (MTV): Neutralization of MTV by Mouse Antiserum

Phyllis B. Blair

Cancer Res 1968;28:148-149.

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