1887

Abstract

Perinatal infection with a temperature-sensitive mutant (ts-1) of Moloney murine leukemia virus (MoMuLV) results in massive splenomegaly and thymomegaly in mice and development of lymphoma in >55 % of infected pups. Previous flow cytometry studies showed a decrease in CD4 cells in perinatally infected pups, but cell population changes in infected animals with lymphoma compared with infected animals without lymphoma has not yet been reported. In the current study, BALB/c mice were infected with ts-1 through breast milk transmission and observed until development of clinical signs and symptoms of lymphoma and/or symptomatic ts-1 infection. Flow cytometry studies were performed on blood, spleen and thymus samples and correlated with gross morphology and histological changes, resulting from the development of lymphoma. Infected animals with lymphoma had significant decreases in CD4 and CD8 cell counts in blood and spleen compared with controls. The spleens of infected animals without lymphoma showed a decrease in CD4 and CD8 cell counts, but this was not significant compared with controls. In the thymus, CD4 and CD8 cell counts also decreased, but this was not significant in infected animals with and without lymphoma compared with controls. Markers of myeloid cell dysfunction increased in the thymus of animals with infection with and without lymphoma compared with controls. Thus, immunosuppression and CD4/CD8 cell decreases in the spleen and thymus are associated with malignant transformation and development of lymphoma in this animal model.

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2012-09-01
2020-01-23
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References

  1. Biggar R. J. , Chaturvedi A. K. , Goedert J. J. , Engels E. A. . HIV/AIDS Cancer Match Study ( 2007; ). AIDS-related cancer and severity of immunosuppression in persons with AIDS. . J Natl Cancer Inst 99:, 962–972. [CrossRef] [PubMed]
    [Google Scholar]
  2. Bower M. , Fisher M. , Hill T. , Reeves I. , Walsh J. , Orkin C. , Phillips A. N. , Bansi L. , Gilson R. . & other authors ( 2009; ). CD4 counts and the risk of systemic non-Hodgkin’s lymphoma in individuals with HIV in the UK. . Haematologica 94:, 875–880. [CrossRef] [PubMed]
    [Google Scholar]
  3. Chakraborty J. , Clark S. , Okonta H. , Duggan J. . ( 2003; ). A small animal model for mother-to-fetus transmission of ts1, a murine retrovirus. . Viral Immunol 16:, 191–201. [CrossRef] [PubMed]
    [Google Scholar]
  4. Chakraborty J. , Okonta H. , Bagalb H. , Lee S. J. , Fink B. , Changanamkandat R. , Duggan J. . ( 2008; ). Retroviral gene insertion in breast milk mediated lymphomagenesis. . Virology 377:, 100–109. [CrossRef]
    [Google Scholar]
  5. Chakraborty J. , Okonta H. , Bagalb H. , Duggan J. . ( 2011; ). MoMuLV-ts-1: a unique mouse model of retrovirus-induced lymphoma transmitted by breast milk. . Adv Virol 2011:, 1–16.[PubMed] [CrossRef]
    [Google Scholar]
  6. Clark S. , Duggan J. , Chakraborty J. . ( 2001; ). tsl and LP-BM5: a comparison of two murine retrovirus models for HIV. . Viral Immunol 14:, 95–109. [CrossRef] [PubMed]
    [Google Scholar]
  7. Craig F. E. , Foon K. A. . ( 2008; ). Flow cytometric immunophenotyping for hematologic neoplasms. . Blood 111:, 3941–3967. [CrossRef] [PubMed]
    [Google Scholar]
  8. Diao J. , Zhao J. , Winter E. , Cattral M. S. . ( 2011; ). Tumors suppress in situ proliferation of cytotoxic T cells by promoting differentiation of Gr-1+ conventional dendritic cells through IL-6. . J Immunol 186:, 5058–5067. [CrossRef] [PubMed]
    [Google Scholar]
  9. Duggan J. , Okonta H. , Chakraborty J. . ( 2004; ). Vertical transmission of a murine retrovirus, ts1. . Viral Immunol 17:, 266–278. [CrossRef] [PubMed]
    [Google Scholar]
  10. Duggan J. , Okonta H. , Chakraborty J. . ( 2006; ). Transmission of Moloney murine leukemia virus (ts-1) by breast milk. . J Gen Virol 87:, 2679–2684. [CrossRef] [PubMed]
    [Google Scholar]
  11. Prasad G. , Stoica G. , Wong P. K. Y. . ( 1989; ). The role of the thymus in the pathogenesis of hind-limb paralysis induced by ts1, a mutant of Moloney murine leukemia virus-TB. . Virology 169:, 332–340. [CrossRef] [PubMed]
    [Google Scholar]
  12. Pulendran B. , Lingappa J. , Kennedy M. K. , Smith J. , Teepe M. , Rudensky A. , Maliszewski C. R. , Maraskovsky E. . ( 1997; ). Developmental pathways of dendritic cells in vivo: distinct function, phenotype, and localization of dendritic cell subsets in FLT3 ligand-treated mice. . J Immunol 159:, 2222–2231.[PubMed]
    [Google Scholar]
  13. Saha K. , Wong P. K. Y. . ( 1991; ). T, not B, lymphocytes are required for immunodeficiency and paralysis induced by ts1, a mutant of Moloney murine leukemia virus-TB. . Virology 183:, 815–820. [CrossRef] [PubMed]
    [Google Scholar]
  14. Saha K. , Wong P. K. Y. . ( 1992a; ). Protective role of cytotoxic lymphocytes against murine leukemia virus-induced neurologic disease and immunodeficiency is enhanced by the presence of helper T cells. . Virology 188:, 921–925. [CrossRef] [PubMed]
    [Google Scholar]
  15. Saha K. , Wong P. K. Y. . ( 1992b; ). ts1, a temperature-sensitive mutant of Moloney murine leukemia virus TB, can infect both CD4+ and CD8+ T cells but requires CD4+ T cells in order to cause paralysis and immunodeficiency. . J Virol 66:, 2639–2646.[PubMed]
    [Google Scholar]
  16. Saha K. , Yuen P. H. , Wong P. K. Y. . ( 1994; ). Murine retrovirus-induced depletion of T cells is mediated through activation-induced death by apoptosis. . J Virol 68:, 2735–2740.[PubMed]
    [Google Scholar]
  17. Wong P. K. Y. . ( 1990; ). Moloney murine leukemia virus temperature-sensitive mutants: a model for retrovirus-induced neurologic disorders. . Curr Top Microbiol Immunol 160:, 29–60. [CrossRef] [PubMed]
    [Google Scholar]
  18. Wong P. K. Y. , Russ L. J. , McCarter J. A. . ( 1973; ). Rapid, selective procedure for isolation of spontaneous temperature-sensitive mutants of Moloney leukemia virus. . Virology 51:, 424–431. [CrossRef] [PubMed]
    [Google Scholar]
  19. Wong P. K. Y. , Prasad G. , Hansen J. , Yuen P. H. . ( 1989; ). ts1, a mutant of Moloney murine leukemia virus-TB, causes both immunodeficiency and neurologic disorders in BALB/c mice. . Virology 170:, 450–459. [CrossRef] [PubMed]
    [Google Scholar]
  20. Wong P. K. , Suzurek P. F. , Floyd E. , Saha K. , Brooks B. R. . ( 1991; ). Alteration from T- to B-cell tropism reduces thymic atrophy and cytocidal effects in thymocytes but not neurovirulence induced by ts1, a mutant of Moloney murine leukemia virus TB. Proc Natl Acad Sci U S A 88, 8991–8995.
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