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
Google Scholar
Right arrow Articles by Yamamoto, T.
Right arrow Articles by Matano, T.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yamamoto, T.
Right arrow Articles by Matano, T.

 Previous Article  |  Next Article 

Journal of Virology, June 2009, p. 5514-5524, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00145-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Polyfunctional CD4+ T-Cell Induction in Neutralizing Antibody-Triggered Control of Simian Immunodeficiency Virus Infection{triangledown}

Takuya Yamamoto,1,2,{dagger} Nami Iwamoto,3,{dagger} Hiroyuki Yamamoto,3,{dagger} Tetsuo Tsukamoto,3 Tetsuya Kuwano,3 Akiko Takeda,3 Miki Kawada,3 Yasuko Tsunetsugu-Yokota,1 and Tetsuro Matano3,4,5*

Department of Immunology,1 AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-Ku, Tokyo 162-8640, Japan,4 Division of Cellular and Molecular Biology,2 International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan,3 Tsukuba Primate Research Center, National Institute of Biomedical Innovation, 1 Hachimandai, Tsukuba 305-0843, Japan5

Received 22 January 2009/ Accepted 6 March 2009

Rapid depletion of memory CD4+ T cells and delayed induction of neutralizing antibody (NAb) responses are characteristics of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections. Although it was speculated that postinfection NAb induction could have only a limited suppressive effect on primary HIV replication, a recent study has shown that a single passive NAb immunization of rhesus macaques 1 week after SIV challenge can result in reduction of viral loads at the set point, indicating a possible contribution of postinfection NAb responses to virus control. However, the mechanism accounting for this NAb-triggered SIV control has remained unclear. Here, we report rapid induction of virus-specific polyfunctional T-cell responses after the passive NAb immunization postinfection. Analysis of SIV Gag-specific responses of gamma interferon, tumor necrosis factor alpha, interleukin-2, macrophage inflammatory protein 1β, and CD107a revealed that the polyfunctionality of Gag-specific CD4+ T cells, as defined by the multiplicity of these responses, was markedly elevated in the acute phase in NAb-immunized animals. In the chronic phase, despite the absence of detectable NAbs, virus control was maintained, accompanied by polyfunctional Gag-specific T-cell responses. These results implicate virus-specific polyfunctional CD4+ T-cell responses in this NAb-triggered virus control, suggesting possible synergism between NAbs and T cells for control of HIV/SIV replication.

* Corresponding author. Mailing address: International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan. Phone: 81-3-6409-2078. Fax: 81-3-6409-2076. E-mail: matano{at}ims.u-tokyo.ac.jp

{triangledown} Published ahead of print on 18 March 2009.

{dagger} T.Y., N.I., and H.Y. contributed equally to this work.

Journal of Virology, June 2009, p. 5514-5524, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00145-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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