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Journal of Virology, March 2002, p. 3007-3014, Vol. 76, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.6.3007-3014.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Induction of Anti-Human Immunodeficiency Virus Type 1 (HIV-1) CD8+ and CD4+ T-Cell Reactivity by Dendritic Cells Loaded with HIV-1 X4-Infected Apoptotic Cells

Xiao-Qing Zhao,1 Xiao-Li Huang, Phalguni Gupta,1,2 Luann Borowski,1 Zheng Fan,1 Simon C. Watkins,3 Elaine K. Thomas,4 and Charles R. Rinaldo, Jr.1,2*

Department of Infectious Diseases and Microbiology, Graduate School of Public Health,1 Departments of Pathology,2 Cell Biology and Physiology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261 ,3 Immunex Corporation, Seattle, Washington 981014

Received 11 July 2001/ Accepted 29 November 2001

T-cell responses to X4 strains of human immunodeficiency virus type 1 (HIV-1) are considered important in controlling progression of HIV-1 infection. We investigated the ability of dendritic cells (DC) and various forms of HIV-1 X4 antigen to induce anti-HIV-1 T-cell responses in autologous peripheral blood mononuclear cells from HIV-1-infected persons. Immature DC loaded with HIV-1 IIIB-infected, autologous, apoptotic CD8- cells and matured with CD40 ligand induced gamma interferon production in autologous CD8+ and CD4+ T cells. In contrast, mature DC loaded with HIV-1 IIIB-infected, necrotic cells or directly infected with cell-free HIV-1 IIIB were poorly immunogenic. Thus, HIV-1-infected cells undergoing apoptosis serve as a rich source of X4 antigen for CD8+ and CD4+ T cells by DC. This may be an important mechanism of HIV-1 immunogenicity and provides a strategy for immunotherapy of HIV-1-infected patients on combination antiretroviral therapy.

* Corresponding author. Mailing address: A427 Crabtree Hall, University of Pittsburgh Graduate School of Public Health, 130 DeSoto St., Pittsburgh, PA 15261. Phone: (412) 624-3928. Fax: (412) 624-4953. E-mail: rinaldo{at}pitt.edu.

Journal of Virology, March 2002, p. 3007-3014, Vol. 76, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.6.3007-3014.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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