Monocyte-derived dendritic cells as a model for the study of HIV-1 infection: productive infection and phenotypic changes during culture in human serum.
Dendritic cells (DC) have been implicated in the initial selection for macrophage-tropic HIV-1 during transmission and in the generation of high-level virus replication during interactions with CD4 T cells. The role of DC as viral reservoirs and the extent of productive infection is unclear, but the ability to generate large numbers of DC from blood monocytes has produced a tractable model for study of DC-HIV-1 interactions. When cultured in granulocyte-macrophage colony stimulating factor and IL-4, sorted CD14+ monocytes rapidly lost phagocytic function for both 93 nm and 977 nm latex particles and developed the surface markers and function of DC. After 7 days, when returned to medium containing human serum without cytokines, some monocyte-derived dendritic cells (MDDC) became adherent, but retained the costimulatory markers CD80 and CD86 and continued to express CD83 and CD40. The MDDC stimulated allogeneic CD4 T cells, did not express new macrophage markers and remained non-phagocytic. With or without TNF-alpha, MDDC generated in cytokines were infected by macrophage and T cell-tropic virus and produced higher reverse transcriptase levels than did the autologous monocyte-derived macrophages (MDM). When added to T cells, the infected MDDC were able to infect T cells with a wider range of viral isolates than were MDM.
Mallon
D F
DF
Immunology Section, Department of Pathology, Fremantle Hospital, Fremantle, Western Australia.
Buck
A
A
Reece
J C
JC
Crowe
S M
SM
Cameron
P U
PU
D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers; D001769:Blood; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D003470:Culture Media / Q000737:chemistry*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000821:virology*; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D016130:Immunophenotyping; D015847:Interleukin-4; D008264:Macrophages / Q000166:cytology; D009000:Monocytes / Q000166:cytology*; D013997:Time Factors
D015703:Antigens, CD; D015415:Biomarkers; D003470:Culture Media; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor