Myeloid and plasmacytoid dendritic cells transfer HIV-1 preferentially to antigen-specific CD4+ T cells.
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.
Loré
Karin
K
Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. klore@mail.nih.gov
Smed-Sörensen
Anna
A
Vasudevan
Jayanand
J
Mascola
John R
JR
Koup
Richard A
RA
D017951:Antigen Presentation / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism; D018845:CD11 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D005434:Flow Cytometry; D005452:Fluoresceins; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D053650:Interleukin-3 Receptor alpha Subunit; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism; D016185:Receptors, Interleukin-3 / Q000276:immunology; D013388:Succinimides
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D000956:Antigens, Viral; D018845:CD11 Antigens; D017931:DNA Primers; D005452:Fluoresceins; C115022:IL3RA protein, human; D016898:Interferon-alpha; D053650:Interleukin-3 Receptor alpha Subunit; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D016185:Receptors, Interleukin-3; D013388:Succinimides