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

 Previous Article  |  Next Article 

Journal of Virology, November 2001, p. 10843-10855, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.10843-10855.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Exogenous Interleukin-2 Administration Corrects the Cell Cycle Perturbation of Lymphocytes from Human Immunodeficiency Virus-Infected Individuals

Mirko Paiardini,1,2 Domenico Galati,3 Barbara Cervasi,1,2 Giuseppe Cannavo,3 Luca Galluzzi,2 Maria Montroni,4 Denise Guetard,5 Mauro Magnani,2 Giuseppe Piedimonte,3 and Guido Silvestri1,*

Vaccine Research Center and Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia1; Istituto di Chimica Biologica "G. Fornaini," Universitá di Urbino, Urbino,2 Dipartimento di Patologia Generale, Malattie Infettive ed Ispezione degli Alimenti, Facoltá di Medicina Veterinaria, and Dipartimento di Igiene, Medicia Preventiva e Sanitá Pubblica, Facoltá di Medicina e Chirurgia, Universitá degli Studi di Messina, Messina,3 and Servizio di Immunologia Clinica, Facoltá di Medicina e Chirurgia, Universitá di Ancona, Ancona,4 Italy; and Unite de Oncologie Virale and Département SIDA et Retrovirus, Institut Pasteur, Paris, France5

Received 21 May 2001/Accepted 30 July 2001

Human immunodeficiency virus (HIV)-induced immunodeficiency is characterized by progressive loss of CD4+ T cells associated with functional abnormalities of the surviving lymphocytes. Increased susceptibility to apoptosis and loss of proper cell cycle control can be observed in lymphocytes from HIV-infected individuals and may contribute to the lymphocyte dysfunction of AIDS patients. To better understand the relation between T-cell activation, apoptosis, and cell cycle perturbation, we studied the effect of exogenous interleukin-2 (IL-2) administration on the intracellular turnover of phase-dependent proteins. Circulating T cells from HIV-infected patients display a marked discrepancy between a metabolic profile typical of G0 and a pattern of expression of phase-dependent proteins that indicates a more-advanced position within the cell cycle. This discrepancy is enhanced by in vitro activation with ConA and ultimately results in a marked increase of apoptotic events. Conversely, treatment of lymphocytes with IL-2 alone restores the phase-specific pattern of expression of cell cycle-dependent proteins and is associated with low levels of apoptosis. Interestingly, exogenous IL-2 administration normalizes the overall intracellular protein turnover, as measured by protein synthesis, half-life of newly synthesised proteins, and total protein ubiquitination, thus providing a possible explanation for the effect of IL-2 on the intracellular kinetics of cell cycle-dependent proteins. The beneficial effect of IL-2 administration is consistent with the possibility of defective IL-2 function in vivo, which is confirmed by the observation that lymphocytes from HIV-infected patients show abnormal endogenous IL-2 paracrine/autocrine function upon in vitro mitogen stimulation. Overall these results confirm that perturbation of cell cycle control contributes to HIV-related lymphocyte dysfunction and, by showing that IL-2 administration can revert this perturbation, suggest a new mechanism of action of IL-2 therapy in HIV-infected patients.

* Corresponding author. Mailing address: Vaccine Research Center and Division of Infectious Diseases, Dept. of Medicine, Emory University, 954 Gatewood Rd. NE, Atlanta, GA 30329. Phone: (404) 712-8113. Fax: (404) 727-8199. E-mail: gsilves{at}rmy.emory.edu.

Journal of Virology, November 2001, p. 10843-10855, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.10843-10855.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Bostik, P., Noble, E. S., Stephenson, S. T., Villinger, F., Ansari, A. A. (2007). CD4+ T Cells from Simian Immunodeficiency Virus Disease-Resistant Sooty Mangabeys Produce More IL-2 Than Cells from Disease-Susceptible Species: Involvement of p300 and CREB at the Proximal IL-2 Promoter in IL-2 Up-Regulation. J. Immunol. 178: 7720-7729 [Abstract] [Full Text]  
  • Paiardini, M., Cervasi, B., Sumpter, B., McClure, H. M., Sodora, D. L., Magnani, M., Staprans, S. I., Piedimonte, G., Silvestri, G. (2006). Perturbations of Cell Cycle Control in T Cells Contribute to the Different Outcomes of Simian Immunodeficiency Virus Infection in Rhesus Macaques and Sooty Mangabeys. J. Virol. 80: 634-642 [Abstract] [Full Text]  
  • Paiardini, M., Cervasi, B., Albrecht, H., Muthukumar, A., Dunham, R., Gordon, S., Radziewicz, H., Piedimonte, G., Magnani, M., Montroni, M., Kaech, S. M., Weintrob, A., Altman, J. D., Sodora, D. L., Feinberg, M. B., Silvestri, G. (2005). Loss of CD127 Expression Defines an Expansion of Effector CD8+ T Cells in HIV-Infected Individuals. J. Immunol. 174: 2900-2909 [Abstract] [Full Text]  
  • Lichterfeld, M., Kaufmann, D. E., Yu, X. G., Mui, S. K., Addo, M. M., Johnston, M. N., Cohen, D., Robbins, G. K., Pae, E., Alter, G., Wurcel, A., Stone, D., Rosenberg, E. S., Walker, B. D., Altfeld, M. (2004). Loss of HIV-1-specific CD8+ T Cell Proliferation after Acute HIV-1 Infection and Restoration by Vaccine-induced HIV-1-specific CD4+ T Cells. JEM 200: 701-712 [Abstract] [Full Text]  
  • Bahbouhi, B., Landay, A., Al-Harthi, L. (2004). Dynamics of cytokine expression in HIV productively infected primary CD4+ T cells. Blood 103: 4581-4587 [Abstract] [Full Text]  
  • Bostik, P., Dodd, G. L., Villinger, F., Mayne, A. E., Ansari, A. A. (2004). Dysregulation of the Polo-Like Kinase Pathway in CD4+ T Cells Is Characteristic of Pathogenic Simian Immunodeficiency Virus Infection. J. Virol. 78: 1464-1472 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»