This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weng, X. Articles by Jolicoeur, P. Search for Related Content PubMed PubMed Citation Articles by Weng, X. Articles by Jolicoeur, P.

 Previous Article  |  Next Article 

Journal of Virology, May 2004, p. 5244-5257, Vol. 78, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.10.5244-5257.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

CD4⁺ T Cells from CD4C/HIV^Nef Transgenic Mice Show Enhanced Activation In Vivo with Impaired Proliferation In Vitro but Are Dispensable for the Development of a Severe AIDS-Like Organ Disease

Xiaoduan Weng,^1, Elena Priceputu,^1, Pavel Chrobak,¹ Johanne Poudrier,¹ Denis G. Kay,¹ Zaher Hanna,¹ Tak W. Mak,² and Paul Jolicoeur^1,3,4*

Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7,¹ Department of Microbiology and Immunology, Université de Montréal, Montreal, Quebec H3C 3J7,³ Division of Experimental Medicine, McGill University, Montreal, Quebec H3G 1A4,⁴ Department of Medical Biophysics and Immunology, Ontario Cancer Institute, University of Toronto, Toronto, Ontario M4X 1K9, Canada²

Received 25 August 2003/ Accepted 16 January 2004

The cellular and molecular mechanisms of dysfunction and depletion of CD4⁺ T lymphocytes over the course of human immunodeficiency virus type 1 (HIV-1) infection are still incompletely understood, but chronic immune activation is thought to play an important role in disease progression. We studied CD4⁺ T-cell biology in CD4C/HIV transgenic (Tg) mice, in which Nef expression is sufficient to induce a severe AIDS-like disease including a preferential decrease of CD4⁺ T cells. We show here that Nef-expressing Tg CD4⁺ T cells exhibit an activated/memory-like phenotype which appears to be independent of antigenic stimulation, as documented in experiments involving breeding with AD10 TcR Tg mice. In addition, in vivo bromodeoxyuridine incorporation showed that a larger proportion of Tg than non-Tg CD4⁺ T cells entered the S phase. However, in vitro, Tg CD4⁺ T cells were found to have a very limited capacity to divide in response to stimulation with anti-CD3 and anti-CD28 or in allogeneic mixed leukocyte reactions. Interestingly, despite these observations, the deletion of Tg CD4⁺ T cells had little impact on the development of other AIDS-like organ phenotypes. Thus, the Nef-induced chronic activation of CD4⁺ T cells may exhaust the T-cell pool and may contribute to the thymic atrophy and the low number of CD4⁺ T cells observed in these Tg mice.

X.W. and E.P. contributed equally to this work.

This article has been cited by other articles:

• Priceputu, E., Hanna, Z., Hu, C., Simard, M.-C., Vincent, P., Wildum, S., Schindler, M., Kirchhoff, F., Jolicoeur, P. (2007). Primary Human Immunodeficiency Virus Type 1 Nef Alleles Show Major Differences in Pathogenicity in Transgenic Mice. J. Virol. 81: 4677-4693 [Abstract] [Full Text]  
• Koenen, P. G. F., Hofhuis, F. M., Oosterwegel, M. A., Tesselaar, K. (2007). T Cell Activation and Proliferation Characteristic for HIV-Nef Transgenic Mice Is Lymphopenia Induced. J. Immunol. 178: 5762-5768 [Abstract] [Full Text]  
• Priceputu, E., Bouallaga, I., Zhang, Y., Li, X., Chrobak, P., Hanna, Z. S., Poudrier, J., Kay, D. G., Jolicoeur, P. (2006). Structurally Distinct Ligand-Binding or Ligand-Independent Notch1 Mutants Are Leukemogenic but Affect Thymocyte Development, Apoptosis, and Metastasis Differently. J. Immunol. 177: 2153-2166 [Abstract] [Full Text]  
• Lewandowski, D., Marquis, M., Aumont, F., Lussier-Morin, A.-C., Raymond, M., Senechal, S., Hanna, Z., Jolicoeur, P., de Repentigny, L. (2006). Altered CD4+ T Cell Phenotype and Function Determine the Susceptibility to Mucosal Candidiasis in Transgenic Mice Expressing HIV-1. J. Immunol. 177: 479-491 [Abstract] [Full Text]  
• Vincent, P., Priceputu, E., Kay, D., Saksela, K., Jolicoeur, P., Hanna, Z. (2006). Activation of p21-activated Kinase 2 and Its Association with Nef Are Conserved in Murine Cells but Are Not Sufficient to Induce an AIDS-like Disease in CD4C/HIV Transgenic Mice. J. Biol. Chem. 281: 6940-6954 [Abstract] [Full Text]  
• Fenard, D., Yonemoto, W., de Noronha, C., Cavrois, M., Williams, S. A., Greene, W. C. (2005). Nef Is Physically Recruited into the Immunological Synapse and Potentiates T Cell Activation Early after TCR Engagement. J. Immunol. 175: 6050-6057 [Abstract] [Full Text]  
• Priceputu, E., Rodrigue, I., Chrobak, P., Poudrier, J., Mak, T. W., Hanna, Z., Hu, C., Kay, D. G., Jolicoeur, P. (2005). The Nef-Mediated AIDS-Like Disease of CD4C/Human Immunodeficiency Virus Transgenic Mice Is Associated with Increased Fas/FasL Expression on T Cells and T-Cell Death but Is Not Prevented in Fas-, FasL-, Tumor Necrosis Factor Receptor 1-, or Interleukin-1{beta}-Converting Enzyme-Deficient or Bcl2-Expressing Transgenic Mice. J. Virol. 79: 6377-6391 [Abstract] [Full Text]  
• Jelley-Gibbs, D. M., Dibble, J. P., Filipson, S., Haynes, L., Kemp, R. A., Swain, S. L. (2005). Repeated stimulation of CD4 effector T cells can limit their protective function. J. Exp. Med. 201: 1101-1112 [Abstract] [Full Text]