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Journal of Virology, April 2001, p. 3581-3589, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.3581-3589.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Characterization of the CD154-Positive and CD40-Positive Cellular Subsets Required for Pathogenesis in Retrovirus-Induced Murine Immunodeficiency

Kathy A. Green, Randolph J. Noelle, Brigit G. Durell, and William R. Green*

Department of Microbiology and Immunology, Dartmouth Medical School and Norris Cotton Cancer Center, Lebanon, New Hampshire 03756

Received 7 September 2000/Accepted 12 January 2001

Genetically susceptible C57BL/6 (B6) mice that are infected with the LP-BM5 isolate of murine retroviruses develop profound splenomegaly, lymphadenopathy, hypergammaglobulinemia, terminal B-cell lymphomas, and an immunodeficiency state bearing many similarities to the pathologies seen in AIDS. Because of these similarities, this syndrome has been called murine AIDS (MAIDS). We have previously shown that CD154 (CD40 ligand)-CD40 molecular interactions are required both for the initiation and progression of MAIDS. Thus, in vivo anti-CD154 monoclonal antibody (MAb) treatment inhibited MAIDS symptoms in LP-BM5-infected wild-type mice when either a short course of anti-CD154 MAb treatment was started on the day of infection or a course was initiated 3 to 4 weeks after LP-BM5 administration, after disease was established. Here, we further characterize this required CD154-CD40 interaction by a series of adoptive transfer experiments designed to elucidate which cellular subsets must express CD154 or CD40 for LP-BM5 to induce MAIDS. Specifically with regard to CD154 expression, MAIDS-insusceptible B6 nude mice reconstituted with highly purified CD4+ T cells from wild-type, but not from CD154 knockout, B6 donors displayed clear MAIDS after LP-BM5 infection. In contrast, nude B6 recipients that received CD8+ T cells from wild-type B6 donors did not develop MAIDS after LP-BM5 infection. B6 CD40 knockout mice, which are also relatively resistant to LP-BM5-induced MAIDS, became susceptible to LP-BM5-induced disease after reconstitution with highly purified wild-type B cells but not after receiving purified wild-type dendritic cells (DC) or a combined CD40+ population composed of DC and macrophages obtained from B6 SCID mouse donors. Based on these and other experiments, we thus conclude that the cellular basis for the requirement for CD154-CD40 interactions for MAIDS induction and progression can be accounted for by CD154 expression on CD4+ T cells and CD40 expression on B cells.

* Corresponding author. Mailing address: Department of Microbiology, Dartmouth Medical School and Norris Cotton Cancer Center, Borwell Building, 1 Medical Center Dr., Lebanon, NH 03756. Phone:(603) 650-8607. Fax: (603) 650-6223. E-mail: William.R.Green{at}Dartmouth.edu.

Journal of Virology, April 2001, p. 3581-3589, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.3581-3589.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Green, K. A., Okazaki, T., Honjo, T., Cook, W. J., Green, W. R. (2008). The Programmed Death-1 and Interleukin-10 Pathways Play a Down-Modulatory Role in LP-BM5 Retrovirus-Induced Murine Immunodeficiency Syndrome. J. Virol. 82: 2456-2469 [Abstract] [Full Text]  
  • Li, W., Green, W. R. (2006). The Role of CD4 T Cells in the Pathogenesis of Murine AIDS.. J. Virol. 80: 5777-5789 [Abstract] [Full Text]  
  • Gaur, A., Green, W. R. (2005). Role of a Cytotoxic-T-Lymphocyte Epitope-Defined, Alternative gag Open Reading Frame in the Pathogenesis of a Murine Retrovirus-Induced Immunodeficiency Syndrome. J. Virol. 79: 4308-4315 [Abstract] [Full Text]  
  • Green, K. A., Ahonen, C. L., Cook, W. J., Green, W. R. (2004). CD40-Associated TRAF 6 Signaling Is Required for Disease Induction in a Retrovirus-Induced Murine Immunodeficiency. J. Virol. 78: 6055-6060 [Abstract] [Full Text]  
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  • Yen, M. H., Lepak, N., Swain, S. L. (2002). Induction of CD4 T Cell Changes in Murine AIDS Is Dependent on Costimulation and Involves a Dysregulation of Homeostasis. J. Immunol. 169: 722-731 [Abstract] [Full Text]  


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