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Journal of Virology, August 2002, p. 7535-7543, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7535-7543.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Different Effects of Nef-Mediated HLA Class I Down-Regulation on Human Immunodeficiency Virus Type 1-Specific CD8+ T-Cell Cytolytic Activity and Cytokine Production

Hiroko Tomiyama,1 Hirofumi Akari,2,3 Akio Adachi,2 and Masafumi Takiguchi1*

Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto 860-0811,1 Department of Virology, The University of Tokushima School of Medicine, Tokushima, 770-8503, Japan,2 Viral Biochemistry Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 208923

Received 28 November 2001/ Accepted 5 May 2002

A previous study using a Nef-defective human immunodeficiency virus type 1 (HIV-1) mutant suggested that Nef-mediated down-regulation of HLA class I on the infected cell surface affects the cytolytic activity of HIV-1-specific cytotoxic T-lymphocyte (CTL) clones for HIV-1-infected primary CD4+ T cells. We confirmed this effect by using a nef-mutant HIV-1 strain (NL-M20A) that expresses a Nef protein which does not induce down-regulation of HLA class I molecules but is otherwise functional. HIV-1-specific CTL clones were not able to kill primary CD4+ T cells infected with a Nef-positive HIV-1 strain (NL-432) but efficiently lysed CD4+ T cells infected with NL-M20A. Interestingly, CTL clones stimulated with NL-432-infected CD4+ T cells were able to produce cytokines, albeit at a lower level than when stimulated with NL-M20A-infected CD4+ T cells. This indicates that Nef-mediated HLA class I down-regulation affects CTL cytokine production to a lesser extent than cytolytic activity. Replication of NL-432 was partially suppressed in a coculture of HIV-1-infected CD4+ T cells and HIV-1-specific CTL clones, while replication of NL-M20A was completely suppressed. These results suggest that HIV-1-specific CD8+ T cells are able to partially suppress the replication of HIV-1 through production of soluble HIV-1-suppressive factors such as chemokines and gamma interferon. These findings may account for the mechanism whereby HIV-1-specific CD8+ T cells are able to partially but not completely control HIV-1 replication in vivo.

* 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, August 2002, p. 7535-7543, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7535-7543.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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