To examine whether a retroviral disease can be controlled in animals in which cells from a resistant strain coexist in a state of immunological tolerance with cells from a susceptible strain, allophenic mice were constructed and infected with LP-BM5 murine leukemia viruses which induce a fatal disorder, termed murine acquired immunodeficiency syndrome (MAIDS), characterized by lymphoproliferation and immunodeficiency in susceptible inbred strains of mice. We found that in two different strain combinations, resistance to MAIDS was contingent on the presence in individual animals of >50% of lymphocytes of resistant strain origin and correlated with reduction or elimination of retrovirus. In contrast, animals harboring substantial, but less than predominant, numbers of genetically resistant lymphocytes developed disease and died within the same time frame as susceptible control mice with uncontained proliferation of retrovirus.
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1 December 1996
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December 01 1996
Induction of Murine Acquired Immunodeficiency Syndrome (MAIDS) in Allophenic Mice Generated from Strains Susceptible and Resistant to Disease
Joan M.G. Sechler,
Joan M.G. Sechler
From the *Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; ‡Department of Obstetrics and Gynecology, Johns Hopkins University, Baltimore, Maryland 21287; §Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and ‖Flow Cytometry Section, Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
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Ann Lawler,
Ann Lawler
From the *Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; ‡Department of Obstetrics and Gynecology, Johns Hopkins University, Baltimore, Maryland 21287; §Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and ‖Flow Cytometry Section, Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
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Janet W. Hartley,
Janet W. Hartley
From the *Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; ‡Department of Obstetrics and Gynecology, Johns Hopkins University, Baltimore, Maryland 21287; §Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and ‖Flow Cytometry Section, Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
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Herbert C. Morse, III,
Herbert C. Morse, III
From the *Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; ‡Department of Obstetrics and Gynecology, Johns Hopkins University, Baltimore, Maryland 21287; §Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and ‖Flow Cytometry Section, Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
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Thomas C. McCarty,
Thomas C. McCarty
From the *Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; ‡Department of Obstetrics and Gynecology, Johns Hopkins University, Baltimore, Maryland 21287; §Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and ‖Flow Cytometry Section, Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
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Ruth Swofford,
Ruth Swofford
From the *Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; ‡Department of Obstetrics and Gynecology, Johns Hopkins University, Baltimore, Maryland 21287; §Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and ‖Flow Cytometry Section, Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
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Amy S. Rosenberg
Amy S. Rosenberg
From the *Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; ‡Department of Obstetrics and Gynecology, Johns Hopkins University, Baltimore, Maryland 21287; §Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and ‖Flow Cytometry Section, Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
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Joan M.G. Sechler
,
Ann Lawler
,
Janet W. Hartley
,
Herbert C. Morse, III
,
Thomas C. McCarty
,
Ruth Swofford
,
Amy S. Rosenberg
From the *Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; ‡Department of Obstetrics and Gynecology, Johns Hopkins University, Baltimore, Maryland 21287; §Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and ‖Flow Cytometry Section, Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
Address correspondence to Dr. Amy S. Rosenberg, 29 Lincoln Drive, Bldg 29A, Rm 2B12, Bethesda, MD 20892.
We gratefully acknowledge Joan Austin and Charles Shifler for expert technical assistance; Jason Yip and Kerstin Cehrs for help in preparing the figures and tables; David Stephany for guidance in flow cytometry analysis; and Gwendolyn Jackson for expert animal care. We thank Jawahar Tiwari for performing the statistical analyses. We thank Dennis Klinman, Elizabeth W. Shores, and Giovanna Tosato for critical reviews of the manuscript.
1Abbreviations used in this paper: BM5def, BM5 defective; HPRT, hypoxanthine phosphoribosyl transferase; MAIDS, murine acquired immunodeficiency syndrome; MCF, mink cell focus-forming; MuLV, murine leukemia virus.
Received:
May 01 1996
Revision Received:
September 18 1996
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1996
J Exp Med (1996) 184 (6): 2101–2108.
Article history
Received:
May 01 1996
Revision Received:
September 18 1996
Citation
Joan M.G. Sechler, Ann Lawler, Janet W. Hartley, Herbert C. Morse, Thomas C. McCarty, Ruth Swofford, Amy S. Rosenberg; Induction of Murine Acquired Immunodeficiency Syndrome (MAIDS) in Allophenic Mice Generated from Strains Susceptible and Resistant to Disease. J Exp Med 1 December 1996; 184 (6): 2101–2108. doi: https://doi.org/10.1084/jem.184.6.2101
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