The Journal of Experimental Medicine
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Published 20 June 2005. doi:10.1084/jem.20042413
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 12, 2023-2033
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ARTICLE

 Myeloid and plasmacytoid dendritic cells transfer HIV-1 preferentially to antigen-specific CD4+ T cells

Karin Loré1, Anna Smed-Sörensen3, Jayanand Vasudevan1, John R. Mascola2, and Richard A. Koup1

1 Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
2 BSL-3 Core Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
3 Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, S-141 86 Stockholm, Sweden

CORRESPONDENCE Karin Loré: klore{at}mail.nih.gov

Dendritic cells (DCs) are essential antigen-presenting cells for the induction of T cell immunity against pathogens such as human immunodeficiency virus (HIV)-1. At the same time, HIV-1 replication is strongly enhanced in DC–T cell clusters, potentially undermining this process. We found that immature CD123+ plasmacytoid DCs (PDCs) and CD11c+ myeloid DCs (MDCs) were susceptible to both a CCR5- and a CXCR4-using HIV-1 isolate in vitro and were able to efficiently transfer that infection to autologous CD4+ T cells. Soon after HIV-1 exposure, both PDCs and MDCs were able to transfer the virus to T cells in the absence of a productive infection. However, once a productive infection was established in the DCs, newly synthesized virus was predominantly spread to T cells. HIV-1 exposure of the MDCs and PDCs did not inhibit their ability to present cytomegalovirus (CMV) antigens and activate CMV-specific memory T cells. As a result, both PDCs and MDCs preferentially transmitted HIV-1 to the responding CMV antigen–specific CD4+ T cells rather than to nonresponding T cells. This suggests that the induction of antigen-specific T cell responses by DCs, a process crucial to immune defense, can lead to preferential HIV-1 infection and the deletion of responding CD4+ T cells.

Abbreviations used: AZT, azidothymidine; CFSE, carboxyfluorescein diacetate succinimidyl ester; MDC, myeloid DC; PDC, plasmacytoid DC; SEB, Staphylococcal enterotoxin B; sssDNA, negative strand strong stop DNA; TLR, Toll-like receptor.


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