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Journal of Virology, June 2006, p. 5777-5789, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.02711-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Role of CD4 T Cells in the Pathogenesis of Murine AIDS

Wen Li¹ and William R. Green^1,2*

Department of Microbiology and Immunology, Dartmouth Medical School,¹ Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03756²

Received 25 December 2005/ Accepted 3 March 2006

LP-BM5, a retroviral isolate, induces a disease featuring retrovirus-induced immunodeficiency, designated murine AIDS (MAIDS). Many of the features of the LP-BM5-induced syndrome are shared with human immunodeficiency virus-induced disease. For example, CD4 T cells are critical to the development of MAIDS. In vivo depletion of CD4 T cells before LP-BM5 infection rendered genetically susceptible B6 mice MAIDS resistant. Similarly, MAIDS did not develop in B6.nude mice. However, if reconstituted with CD4 T cells, B6.nude mice develop full-blown MAIDS. Our laboratory has shown that the interaction of B and CD4 T cells that is central to MAIDS pathogenesis requires ligation of CD154 on CD4 T cells with CD40 on B cells. However, it is not clear which additional characteristics of the phenotypically and functionally heterogeneous CD4 T-cell compartment are required. Here, in vivo adoptive transfer experiments using B6.nude recipients are employed to compare the pathogenic abilities of CD4 T-cell subsets defined on the basis of cell surface phenotypic or functional differences. Th1 and Th2 CD4 T cells equally supported MAIDS induction. The rare Thy1.2^– CD4 subset that expands upon LP-BM5 infection was not necessary for MAIDS. Interestingly, CD45RB^low CD4 T cells supported significantly less disease than CD45RB^high CD4 T cells. Because the decreased MAIDS pathogenesis could not be attributed to inhibition by CD45RB^low CD25⁺ natural T-regulatory cells, an intrinsic property of the CD45RB^low cells appeared responsible. Similarly, there was no evidence that natural T-regulatory cells played a role in LP-BM5-induced pathogenesis in the context of the intact CD4 T-cell population.

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* Corresponding author. Mailing address: Department of Microbiology and Immunology, Dartmouth Medical School, 603W Borwell Research Building, One Medical Center Drive, Lebanon, NH 03756. Phone: (603) 650-8607. Fax: (603) 650-6223. E-mail: william.r.green{at}dartmouth.edu.

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Journal of Virology, June 2006, p. 5777-5789, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.02711-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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