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Journal of Virology, June 2009, p. 6288-6299, Vol. 83, No. 12
0022-538X/09/$08.00+0     doi:10.1128/JVI.02611-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Primary Human Immunodeficiency Virus Type 1-Specific CD8+ T-Cell Responses Induced by Myeloid Dendritic Cells{triangledown}

Bonnie A. Colleton ,1,{dagger},{ddagger} Xiao-Li Huang,1,{dagger} Nada M. Melhem,1,§ Zheng Fan,1 Luann Borowski,1 Giovanna Rappocciolo,1 and Charles R. Rinaldo1,2*

Graduate School of Public Health,1 School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania2

Received 17 December 2008/ Accepted 25 March 2009

Induction of an antigenically broad and vigorous primary T-cell immune response by myeloid dendritic cells (DC) in blood and tissues could be important for an effective prophylactic or therapeutic vaccine to human immunodeficiency virus type 1 (HIV-1). Here we show that a primary CD8+ T-cell response can be induced by HIV-1 peptide-loaded DC derived from blood monocytes of HIV-1-negative adults and neonates (moDC) and by Langerhans cells (LC) and interstitial, dermal-intestinal DC (idDC) derived from CD34+ stem cells of neonatal cord blood. Optimal priming of single-cell gamma interferon (IFN-{gamma}) production by CD8+ T cells required CD4+ T cells and was broadly directed to multiple regions of Gag, Env, and Nef that corresponded to known and predicted major histocompatibility complex class I epitopes. Polyfunctional CD8+ T-cell responses, defined as single-cell production of more than one cytokine (IFN-{gamma}, interleukin 2, or tumor necrosis factor alpha), chemokine (macrophage inhibitory factor 1β), or cytotoxic degranulation marker CD107a, were primed by moDC, LC, and idDC to HIV-1 Gag and reverse transcriptase epitopes, as well as to Epstein-Barr virus and influenza A virus epitopes. Thus, three major types of blood and tissue myeloid DC targeted by HIV-1, i.e., moDC, LC, and idDC, can prime multispecific, polyfunctional CD8+ T-cell responses to HIV-1 and other viral antigens.

* Corresponding author. Mailing address: A419 Crabtree Hall, University of Pittsburgh Graduate School of Public Health, 130 DeSoto Street, Pittsburgh, PA 15261. Phone: (412) 624-3928. Fax: (412) 624-4953. E-mail: rinaldo{at}pitt.edu

{triangledown} Published ahead of print on 8 April 2009.

{dagger} These authors contributed equally to this work.

{ddagger} Present address: Pennsylvania State University, M.S. Hershey Medical Center College of Medicine, Department of Public Health Sciences, 600 Centerview Drive, Hershey, PA 17033.

§ Present address: Medical Laboratory Technology Program, Faculty of Health Sciences, American University of Beirut, 333 Van Dyck Bldg, 11-0236 Riad El Solh 1107-2020, Beirut, Lebanon.

Journal of Virology, June 2009, p. 6288-6299, Vol. 83, No. 12
0022-538X/09/$08.00+0     doi:10.1128/JVI.02611-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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