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 Malhotra, U.
Right arrow Articles by McElrath, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Malhotra, U.
Right arrow Articles by McElrath, M. J.

 Previous Article  |  Next Article 

Journal of Virology, February 2003, p. 2663-2674, Vol. 77, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.4.2663-2674.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Early Induction and Maintenance of Env-Specific T-Helper Cells following Human Immunodeficiency Virus Type 1 Infection

Uma Malhotra,1,2 Sarah Holte,3 Tuofu Zhu,4,5 Elizabeth Delpit,4 Claire Huntsberry,1 Alessandro Sette,6 Raj Shankarappa,7 Janine Maenza,1,3 Lawrence Corey,1,3,4 and M. Juliana McElrath1,3,4*

Program in Infectious Diseases, Clinical Research Division,1 Program in Biostatistics, Public Health Sciences Division,3 Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, and Department of Medicine,2 Department of Laboratory Medicine,4 Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195,5 Epimmune, San Diego, California 92121,6 Allegheny-Singer Research Institute, Pittsburgh, Pennsylvania7

Received 20 June 2002/ Accepted 18 November 2002

Mounting evidence points to a role for CD4+ T-helper (Th) cell activities in controlling human immunodeficiency virus type 1 (HIV-1) infection. To determine the induction and evolution of Th responses following acute infection, we prospectively analyzed Env- and Gag-specific Th responses longitudinally for 92 patients with acute (n = 28) or early (n = 64) HIV-1 infection (median, 55 days postinfection [DPI]). The probability of detecting HIV-1-specific lymphoproliferative responses was remarkably low, and when present, the responses were more likely to be Gag specific than Env specific (16 versus 5%). Env-specific responses were significantly more common in patients presenting at <30 DPI than in those presenting at 30 to 365 DPI (21 versus 0.5%, P = 0.001). By contrast, Gag-specific responses occurred with similar frequencies among subjects presenting at <30 DPI and 30 to 365 DPI (13 versus 17%, P = 0.6). After treatment, and regardless of the duration of infection before therapy, Gag-specific Th responses predominated. Furthermore, some acutely infected subjects lost detectable Env-specific Th proliferative responses, which failed to reemerge upon treatment. Detailed analysis for one such subject revealed Env-specific lymphoproliferation at 11 DPI but no detectable Env-specific lymphoproliferation or ex vivo gamma interferon (IFN-{gamma}) secretion at multiple subsequent time points. Env-specific CD4+ T-cell clones from 11 DPI recognized six epitopes in both conserved and variable regions within gp120 and gp41, exhibited major histocompatibility complex-restricted cytotoxicity, and secreted high levels of antiviral cytokines. T-cell receptor clonal transcript analyses and autologous virus sequencing revealed that Th cells induced during acute infection were maintained and there were no Th escape mutations. Subsequent analysis for this subject and six of seven others revealed detectable IFN-{gamma}-secreting cells, but only following in vitro gp160 stimulation. In summary, we conclude that Env-specific Th responses are elicited very early in acute infection and may precede Gag-specific responses. The inability to detect Env-specific Th responses over time and despite antiretroviral therapy may reflect low frequencies and impaired proliferative capacity, and viral escape is not necessary for this to occur.

* Corresponding author. Mailing address: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., D3-100, Seattle, WA 98109. Phone: (206) 667-6704. Fax: (206) 667-4411. E-mail: kd{at}u.washington.edu.

Journal of Virology, February 2003, p. 2663-2674, Vol. 77, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.4.2663-2674.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gaseitsiwe, S., Valentini, D., Ahmed, R., Mahdavifar, S., Magalhaes, I., Zerweck, J., Schutkowski, M., Gautherot, E., Montero, F., Ehrnst, A., Reilly, M., Maeurer, M. (2009). Major Histocompatibility Complex Class II Molecule-Human Immunodeficiency Virus Peptide Analysis Using a Microarray Chip. CVI 16: 567-573 [Abstract] [Full Text]  
  • Li, H., Chien, P. C. Jr., Tuen, M., Visciano, M. L., Cohen, S., Blais, S., Xu, C.-F., Zhang, H.-T., Hioe, C. E. (2008). Identification of an N-Linked Glycosylation in the C4 Region of HIV-1 Envelope gp120 That Is Critical for Recognition of Neighboring CD4 T Cell Epitopes. J. Immunol. 180: 4011-4021 [Abstract] [Full Text]  
  • Malhotra, U., Li, F., Nolin, J., Allison, M., Zhao, H., Mullins, J. I., Self, S., McElrath, M. J. (2007). Enhanced Detection of Human Immunodeficiency Virus Type 1 (HIV-1) Nef-Specific T Cells Recognizing Multiple Variants in Early HIV-1 Infection. J. Virol. 81: 5225-5237 [Abstract] [Full Text]  
  • Cohen, W. M., Pouvelle-Moratille, S., Wang, X.-F., Farci, S., Munier, G., Charron, D., Menez, A., Busson, M., Maillere, B. (2006). Scanning the HIV Genome for CD4+ T Cell Epitopes Restricted to HLA-DP4, the Most Prevalent HLA Class II Molecule. J. Immunol. 176: 5401-5408 [Abstract] [Full Text]  
  • Zaunders, J. J., Munier, M. L., Kaufmann, D. E., Ip, S., Grey, P., Smith, D., Ramacciotti, T., Quan, D., Finlayson, R., Kaldor, J., Rosenberg, E. S., Walker, B. D., Cooper, D. A., Kelleher, A. D., on behalf of the PHAEDRA Study Team, (2005). Early proliferation of CCR5+ CD38+++ antigen-specific CD4+ Th1 effector cells during primary HIV-1 infection. Blood 106: 1660-1667 [Abstract] [Full Text]  
  • Kaufmann, D. E., Bailey, P. M., Sidney, J., Wagner, B., Norris, P. J., Johnston, M. N., Cosimi, L. A., Addo, M. M., Lichterfeld, M., Altfeld, M., Frahm, N., Brander, C., Sette, A., Walker, B. D., Rosenberg, E. S. (2004). Comprehensive Analysis of Human Immunodeficiency Virus Type 1-Specific CD4 Responses Reveals Marked Immunodominance of gag and nef and the Presence of Broadly Recognized Peptides. J. Virol. 78: 4463-4477 [Abstract] [Full Text]  
  • Day, C. L., Walker, B. D. (2003). Progress in Defining CD4 Helper Cell Responses in Chronic Viral Infections. JEM 198: 1773-1777 [Full Text]  
  • Cao, J., McNevin, J., Malhotra, U., McElrath, M. J. (2003). Evolution of CD8+ T Cell Immunity and Viral Escape Following Acute HIV-1 Infection. J. Immunol. 171: 3837-3846 [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»