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 Zaunders, J. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zaunders, J. J.

 Previous Article  |  Next Article 

Journal of Virology, October 2006, p. 10162-10172, Vol. 80, No. 20
0022-538X/06/$08.00+0     doi:10.1128/JVI.00249-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Infection of CD127+ (Interleukin-7 Receptor+) CD4+ Cells and Overexpression of CTLA-4 Are Linked to Loss of Antigen-Specific CD4 T Cells during Primary Human Immunodeficiency Virus Type 1 Infection

John J. Zaunders,1* Susanna Ip,1,2 Mee Ling Munier,1,2 Daniel E. Kaufmann,3 Kazuo Suzuki,1 Choechoe Brereton,1 Sarah C. Sasson,1,2 Nabila Seddiki,4 Kersten Koelsch,1,2 Alan Landay,5 Pat Grey,2 Robert Finlayson,6 John Kaldor,2 Eric S. Rosenberg,3 Bruce D. Walker,3 Barbara Fazekas de St. Groth,4 David A. Cooper,1,2 Anthony D. Kelleher,1,2 on Behalf of the PHAEDRA Study Team,{dagger}

Centre for Immunology, St. Vincent's Hospital, Sydney, NSW, Australia,1 National Centre in HIV Epidemiology and Clinical Research, University of NSW, Sydney, NSW, Australia,2 Partners AIDS Research Center, Massachusetts General Hospital, Boston, Massachusetts,3 Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW, Australia,4 Rush University, Chicago, Illinois,5 Taylor Square Private Clinic, Sydney, NSW, Australia6

Received 3 February 2006/ Accepted 6 July 2006

We recently found that human immunodeficiency virus (HIV)-specific CD4+ T cells express coreceptor CCR5 and activation antigen CD38 during early primary HIV-1 infection (PHI) but then rapidly disappear from the circulation. This cell loss may be due to susceptibility to infection with HIV-1 but could also be due to inappropriate apoptosis, an expansion of T regulatory cells, trafficking out of the circulation, or dysfunction. We purified CD38+++CD4+ T cells from peripheral blood mononuclear cells, measured their level of HIV-1 DNA by PCR, and found that about 10% of this population was infected. However, a small subset of HIV-specific CD4+ T cells also expressed CD127, a marker of long-term memory cells. Purified CD127+CD4+ lymphocytes contained fivefold more copies of HIV-1 DNA per cell than did CD127-negative CD4+ cells, suggesting preferential infection of long-term memory cells. We observed no apoptosis of antigen-specific CD4+ T cells in vitro and only a small increase in CD45RO+CD25+CD127dimCD4+ T regulatory cells during PHI. However, 40% of CCR5+CD38+++ CD4+ T cells expressed gut-homing integrins, suggesting trafficking through gut-associated lymphoid tissue (GALT). Furthermore, 80% of HIV-specific CD4+ T cells expressed high levels of the negative regulator CTLA-4 in response to antigen stimulation in vitro, which was probably contributing to their inability to produce interleukin-2 and proliferate. Taken together, the loss of HIV-specific CD4+ T cells is associated with a combination of an infection of CCR5+ CD127+ memory CD4+ T cells, possibly in GALT, and a high expression of the inhibitory receptor CTLA-4.

* Corresponding author. Mailing address: Centre for Immunology, St. Vincent's Hospital, Victoria St., Darlinghurst, NSW 2010, Australia. Phone: 61-2-8382-3700. Fax: 61-2-8382-2391. E-mail: j.zaunders{at}cfi.unsw.edu.au.

{dagger} Members of the PHAEDRA Study Team are P. Grey, J. Kaldor, D. A. Cooper, T. Ramacciotti, K. Petoumenos, D. Smith, M. Bloch, N. Medland, R. Finlayson, A. McFarlane, N. J. Roth, C. Workman, A. Carr, A. D. Kelleher, J. Zaunders, and P. Cunningham.

Journal of Virology, October 2006, p. 10162-10172, Vol. 80, No. 20
0022-538X/06/$08.00+0     doi:10.1128/JVI.00249-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kaufmann, D. E., Walker, B. D. (2009). PD-1 and CTLA-4 Inhibitory Cosignaling Pathways in HIV Infection and the Potential for Therapeutic Intervention. J. Immunol. 182: 5891-5897 [Abstract] [Full Text]  
  • Koopman, G., Mortier, D., Hofman, S., Koutsoukos, M., Bogers, W. M. J. M., Wahren, B., Voss, G., Heeney, J. L. (2009). Acute-phase CD4+ T-cell proliferation and CD152 upregulation predict set-point virus replication in vaccinated simian-human immunodeficiency virus strain 89.6p-infected macaques. J. Gen. Virol. 90: 915-926 [Abstract] [Full Text]  
  • Liu, J., Gong, N., Huang, X., Reynolds, A. D., Mosley, R. L., Gendelman, H. E. (2009). Neuromodulatory Activities of CD4+CD25+ Regulatory T Cells in a Murine Model of HIV-1-Associated Neurodegeneration. J. Immunol. 182: 3855-3865 [Abstract] [Full Text]  
  • Nyakeriga, A. M., Fichtenbaum, C. J., Goebel, J., Nicolaou, S. A., Conforti, L., Chougnet, C. A. (2009). Engagement of the CD4 Receptor Affects the Redistribution of Lck to the Immunological Synapse in Primary T Cells: Implications for T-Cell Activation during Human Immunodeficiency Virus Type 1 Infection. J. Virol. 83: 1193-1200 [Abstract] [Full Text]  
  • Ndhlovu, L. C., Loo, C. P., Spotts, G., Nixon, D. F., Hecht, F. M. (2008). FOXP3 expressing CD127lo CD4+ T cells inversely correlate with CD38+ CD8+ T cell activation levels in primary HIV-1 infection. J. Leukoc. Biol. 83: 254-262 [Abstract] [Full Text]  
  • Alvarez, R., Reading, J., King, D. F. L., Hayes, M., Easterbrook, P., Farzaneh, F., Ressler, S., Yang, F., Rowley, D., Vyakarnam, A. (2008). WFDC1/ps20 Is a Novel Innate Immunomodulatory Signature Protein of Human Immunodeficiency Virus (HIV)-Permissive CD4+ CD45RO+ Memory T Cells That Promotes Infection by Upregulating CD54 Integrin Expression and Is Elevated in HIV Type 1 Infection. J. Virol. 82: 471-486 [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»