Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1994 Sep;68(9):5819–5824. doi: 10.1128/jvi.68.9.5819-5824.1994

Murine AIDS is an antigen-driven disease: requirements for major histocompatibility complex class II expression and CD4+ T cells.

N A Giese 1, T Giese 1, H C Morse 3rd 1
PMCID: PMC236986  PMID: 7914549

Abstract

Murine AIDS (MAIDS) is a complex syndrome of lymphoproliferation and immunodeficiency induced by a replication-defective murine leukemia virus (BM5def) that encodes Pr60gag as its only product. It has been suggested that the gag polyprotein is responsible for vigorous antigenic stimulation of CD4+ T cells and generalized secondary activation of the immune system. This model was tested first by infecting mice (C2K/O) that lack class II major histocompatibility complex molecules required for presentation of antigens to CD4+ T cells. C2K/O mice expressed BM5def at high levels but did not develop MAIDS either when unmanipulated or following transfer of CD4+ T cells. Second, B6 mice reconstituted with C2K/O bone marrow cells had normal frequencies of B cells (class II negative) and CD4+ cells and expressed high levels of BM5def transcripts but did not develop MAIDS; however, MAIDS developed in class II-competent nu/nu mice reconstituted with CD4+ T cells and in C2K/O mice reconstituted with B6 bone marrow to give class II-positive B cells and with purified CD4+ T cells. These results indicate that induction of MAIDS by BM5def is antigen driven and is dependent on expression of major histocompatibility complex class II molecules on antigen-presenting cells and the presence of CD4+ T cells.

Full text

PDF
5819

Images in this article

5820Image
on p.5820

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aziz D. C., Hanna Z., Jolicoeur P. Severe immunodeficiency disease induced by a defective murine leukaemia virus. Nature. 1989 Apr 6;338(6215):505–508. doi: 10.1038/338505a0. [DOI] [PubMed] [Google Scholar]
  2. Cerny A., Hügin A. W., Hardy R. R., Hayakawa K., Zinkernagel R. M., Makino M., Morse H. C., 3rd B cells are required for induction of T cell abnormalities in a murine retrovirus-induced immunodeficiency syndrome. J Exp Med. 1990 Jan 1;171(1):315–320. doi: 10.1084/jem.171.1.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chattopadhyay S. K., Sengupta D. N., Fredrickson T. N., Morse H. C., 3rd, Hartley J. W. Characteristics and contributions of defective, ecotropic, and mink cell focus-inducing viruses involved in a retrovirus-induced immunodeficiency syndrome of mice. J Virol. 1991 Aug;65(8):4232–4241. doi: 10.1128/jvi.65.8.4232-4241.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gazzinelli R. T., Eltoum I., Wynn T. A., Sher A. Acute cerebral toxoplasmosis is induced by in vivo neutralization of TNF-alpha and correlates with the down-regulated expression of inducible nitric oxide synthase and other markers of macrophage activation. J Immunol. 1993 Oct 1;151(7):3672–3681. [PubMed] [Google Scholar]
  5. Giese T., Davidson W. F. Evidence for early onset, polyclonal activation of T cell subsets in mice homozygous for lpr. J Immunol. 1992 Nov 1;149(9):3097–3106. [PubMed] [Google Scholar]
  6. Gilmore G. L., Cowing C., Mosier D. E. LP-BM5 murine retrovirus-induced immunodeficiency disease in allogeneic SCID chimeric mice. Inability to recognize a putative viral superantigen does not prevent induction of disease. J Immunol. 1993 Jan 1;150(1):185–189. [PubMed] [Google Scholar]
  7. Grusby M. J., Johnson R. S., Papaioannou V. E., Glimcher L. H. Depletion of CD4+ T cells in major histocompatibility complex class II-deficient mice. Science. 1991 Sep 20;253(5026):1417–1420. doi: 10.1126/science.1910207. [DOI] [PubMed] [Google Scholar]
  8. Hartley J. W., Fredrickson T. N., Yetter R. A., Makino M., Morse H. C., 3rd Retrovirus-induced murine acquired immunodeficiency syndrome: natural history of infection and differing susceptibility of inbred mouse strains. J Virol. 1989 Mar;63(3):1223–1231. doi: 10.1128/jvi.63.3.1223-1231.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Holmes K. L., Morse H. C., 3rd, Makino M., Hardy R. R., Hayakawa K. A unique subset of normal murine CD4+ T cells lacking Thy-1 is expanded in a murine retrovirus-induced immunodeficiency syndrome, MAIDS. Eur J Immunol. 1990 Dec;20(12):2783–2787. doi: 10.1002/eji.1830201237. [DOI] [PubMed] [Google Scholar]
  10. Huang M., Simard C., Jolicoeur P. Susceptibility of inbred strains of mice to murine AIDS (MAIDS) correlates with target cell expansion and high expression of defective MAIDS virus. J Virol. 1992 Apr;66(4):2398–2406. doi: 10.1128/jvi.66.4.2398-2406.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hügin A. W., Vacchio M. S., Morse H. C., 3rd A virus-encoded "superantigen" in a retrovirus-induced immunodeficiency syndrome of mice. Science. 1991 Apr 19;252(5004):424–427. doi: 10.1126/science.1850169. [DOI] [PubMed] [Google Scholar]
  12. Jolicoeur P. Murine acquired immunodeficiency syndrome (MAIDS): an animal model to study the AIDS pathogenesis. FASEB J. 1991 Jul;5(10):2398–2405. doi: 10.1096/fasebj.5.10.2065888. [DOI] [PubMed] [Google Scholar]
  13. Klinman D. M., Morse H. C., 3rd Characteristics of B cell proliferation and activation in murine AIDS. J Immunol. 1989 Feb 15;142(4):1144–1149. [PubMed] [Google Scholar]
  14. Kruisbeek A. M., Mond J. J., Fowlkes B. J., Carmen J. A., Bridges S., Longo D. L. Absence of the Lyt-2-,L3T4+ lineage of T cells in mice treated neonatally with anti-I-A correlates with absence of intrathymic I-A-bearing antigen-presenting cell function. J Exp Med. 1985 May 1;161(5):1029–1047. doi: 10.1084/jem.161.5.1029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Markowitz J. S., Auchincloss H., Jr, Grusby M. J., Glimcher L. H. Class II-positive hematopoietic cells cannot mediate positive selection of CD4+ T lymphocytes in class II-deficient mice. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2779–2783. doi: 10.1073/pnas.90.7.2779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Miltenyi S., Müller W., Weichel W., Radbruch A. High gradient magnetic cell separation with MACS. Cytometry. 1990;11(2):231–238. doi: 10.1002/cyto.990110203. [DOI] [PubMed] [Google Scholar]
  17. Morse H. C., 3rd, Chattopadhyay S. K., Makino M., Fredrickson T. N., Hügin A. W., Hartley J. W. Retrovirus-induced immunodeficiency in the mouse: MAIDS as a model for AIDS. AIDS. 1992 Jul;6(7):607–621. doi: 10.1097/00002030-199207000-00001. [DOI] [PubMed] [Google Scholar]
  18. Mosier D. E., Yetter R. A., Morse H. C., 3rd Functional T lymphocytes are required for a murine retrovirus-induced immunodeficiency disease (MAIDS). J Exp Med. 1987 Jun 1;165(6):1737–1742. doi: 10.1084/jem.165.6.1737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rocha B., von Boehmer H. Peripheral selection of the T cell repertoire. Science. 1991 Mar 8;251(4998):1225–1228. doi: 10.1126/science.1900951. [DOI] [PubMed] [Google Scholar]
  20. Rowe W. P., Pugh W. E., Hartley J. W. Plaque assay techniques for murine leukemia viruses. Virology. 1970 Dec;42(4):1136–1139. doi: 10.1016/0042-6822(70)90362-4. [DOI] [PubMed] [Google Scholar]
  21. Svetić A., Finkelman F. D., Jian Y. C., Dieffenbach C. W., Scott D. E., McCarthy K. F., Steinberg A. D., Gause W. C. Cytokine gene expression after in vivo primary immunization with goat antibody to mouse IgD antibody. J Immunol. 1991 Oct 1;147(7):2391–2397. [PubMed] [Google Scholar]
  22. Yetter R. A., Buller R. M., Lee J. S., Elkins K. L., Mosier D. E., Fredrickson T. N., Morse H. C., 3rd CD4+ T cells are required for development of a murine retrovirus-induced immunodeficiency syndrome (MAIDS). J Exp Med. 1988 Aug 1;168(2):623–635. doi: 10.1084/jem.168.2.623. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES