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 Potter, S. J.
Right arrow Articles by Chakrabarti, L. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Potter, S. J.
Right arrow Articles by Chakrabarti, L. A.

 Previous Article  |  Next Article 

Journal of Virology, December 2007, p. 13904-13915, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01401-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Preserved Central Memory and Activated Effector Memory CD4+ T-Cell Subsets in Human Immunodeficiency Virus Controllers: an ANRS EP36 Study{triangledown}

Simon J. Potter,1,{dagger} Christine Lacabaratz,2,{ddagger} Olivier Lambotte,2,3,{ddagger} Santiago Perez-Patrigeon,1 Benoît Vingert,1 Martine Sinet,2 Jean-Hervé Colle,1 Alejandra Urrutia,2 Daniel Scott-Algara,4 Faroudy Boufassa,5 Jean-François Delfraissy,2,3 Jacques Thèze,1 Alain Venet,2 and Lisa A. Chakrabarti1*

Unité d'Immunogénétique Cellulaire, Institut Pasteur, Paris,1 Institut National de la Santé et de la Recherche Médicale U 802, Université Paris XI,2 Service de Médecine Interne et Maladies Infectieuses, AP-HP, Centre Hospitalo-Universitaire de Bicêtre, Bicêtre,3 Unité des Régulations des Infections Rétrovirales, Institut Pasteur, Paris,4 Institut National de la Santé et de la Recherche Médicale U 822, Centre Hospitalo-Universitaire de Bicêtre, Bicêtre, France5

Received 27 June 2007/ Accepted 26 September 2007

Human immunodeficiency virus (HIV) controllers are rare individuals who spontaneously control HIV type 1 replication for 10 years or more in the absence of antiretroviral treatment. In the present study, HIV controllers (n = 11) maintained potent HIV-specific CD4 responses in spite of very low antigenic loads. Their CD4+ central memory T (TCM) cells were characterized by near-normal numbers and preserved interleukin-2 (IL-2) secretion in response to HIV antigens and uniformly high expression of the survival receptor IL-7 receptor {alpha} (IL-7R{alpha}). Controllers expressed CCR7 at higher levels than uninfected controls, suggesting differences in TCM-cell homing patterns. CD4+ effector memory T (TEM)-cell responses were polyfunctional in HIV controllers, while IL-2 secretion was lost in viremic patients. Cytokine production was three times higher in controllers than in treated patients with undetectable viral loads, suggesting an intrinsically more efficient response in the former group. The total CD4+ TEM-cell pool underwent immune activation in controllers, as indicated by increased HLA-DR expression, decreased IL-7R{alpha} expression, a bias towards gamma interferon production upon polyclonal stimulation, and increased macrophage inflammatory protein 1ß secretion associated with chronic CCR5 down-regulation. Thus, HIV controllers showed a preserved CD4+ TCM-cell compartment and signs of potent functional activation in the CD4+ TEM-cell compartment. While controllers did not show the generalized immune activation pattern associated with disease progression, they had signs of immune activation restricted to the effector compartment. These findings suggest the induction of an efficient, nondetrimental type of immune activation in patients who spontaneously control HIV.

* Corresponding author. Mailing address: Unité d'Immunogénétique Cellulaire, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France. Phone: 33 (1) 44 38 91 31. Fax: 33 (1) 45 68 88 38. E-mail: chakra{at}pasteur.fr

{triangledown} Published ahead of print on 17 October 2007.

{dagger} Present address: Centre for Virus Research, Westmead Millenium Institute, Sydney, Australia.

{ddagger} C.L. and O.L. contributed equally to this study.

Journal of Virology, December 2007, p. 13904-13915, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01401-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Poonia, B., Salvato, M. S., Yagita, H., Maeda, T., Okumura, K., Pauza, C. D. (2009). Treatment with anti-FasL antibody preserves memory lymphocytes and virus-specific cellular immunity in macaques challenged with simian immunodeficiency virus. Blood 114: 1196-1204 [Abstract] [Full Text]  
  • Ferre, A. L., Hunt, P. W., Critchfield, J. W., Young, D. H., Morris, M. M., Garcia, J. C., Pollard, R. B., Yee, H. F. Jr, Martin, J. N., Deeks, S. G., Shacklett, B. L. (2009). Mucosal immune responses to HIV-1 in elite controllers: a potential correlate of immune control. Blood 113: 3978-3989 [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»