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Journal of Virology, October 2005, p. 12536-12543, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12536-12543.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Patterns of Cytokine Production in Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Human CD8+ T Cells after Stimulation with HIV-1-Infected CD4+ T Cells

Mamoru Fujiwara,1 Hiroshi Takata,1 Shinichi Oka,2 Hiroko Tomiyama,1 and Masafumi Takiguchi1*

Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811,1 AIDS Clinical Center, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan2

Received 22 April 2005/ Accepted 6 July 2005

Although human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells can produce various cytokines that suppress HIV-1 replication or modulate anti-HIV-1 immunity, the extent to which HIV-1-specific CD8+ T cells produce cytokines when they recognize HIV-1-infected CD4+ T cells in vivo still remains unclear. We first analyzed the abilities of 10 cytotoxic T-lymphocyte (CTL) clones specific for three HIV-1 epitopes to produce gamma interferon, macrophage inflammatory protein 1ß, and tumor necrosis factor alpha after stimulation with epitope peptide-pulsed cells. These CTL clones produced these cytokines in various combinations within the same specificity and among the different specificities, suggesting a functional heterogeneity of HIV-1-specific effector CD8+ T cells in cytokine production. In contrast, the HIV-1-specific CTL clones for the most part produced a single cytokine, without heterogeneity of cytokine production among the clones, after stimulation with HIV-1-infected CD4+ T cells. The loss of heterogeneity in cytokine production may be explained by low surface expression of HLA class I-epitope peptide complexes. Freshly isolated HIV-1-specific CD8+ T cells with an effector/memory or memory phenotype produced much more of the cytokines than the same epitope-specific CTL clones when stimulated with HIV-1-infected CD4+ T cells. Cytokine production from HIV-1-specific memory/effector and memory CD8+ T cells might be a critical event in the eradication of HIV-1 in HIV-1-infected individuals.

* Corresponding author. Mailing address: Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan. Phone: 81-96-373-6529. Fax: 81-96-373-6532. E-mail: masafumi{at}kaiju.medic.kumamoto-u.ac.jp.

Journal of Virology, October 2005, p. 12536-12543, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12536-12543.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zheng, N., Fujiwara, M., Ueno, T., Oka, S., Takiguchi, M. (2009). Strong Ability of Nef-Specific CD4+ Cytotoxic T Cells To Suppress Human Immunodeficiency Virus Type 1 (HIV-1) Replication in HIV-1-Infected CD4+ T Cells and Macrophages. J. Virol. 83: 7668-7677 [Abstract] [Full Text]  
  • Fujiwara, M., Takiguchi, M. (2007). HIV-1 specific CTLs effectively suppress replication of HIV-1 in HIV-1 infected macrophages. Blood 109: 4832-4838 [Abstract] [Full Text]  
  • Takata, H., Takiguchi, M. (2006). Three Memory Subsets of Human CD8+ T Cells Differently Expressing Three Cytolytic Effector Molecules. J. Immunol. 177: 4330-4340 [Abstract] [Full Text]  


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