CD4+ blood dendritic cells are potent producers of IFN-alpha in response to in vitro HIV-1 infection.
We determined the relative abilities of cell subpopulations from all major PBMC lineages of normal donors to produce IFN-alpha in response to in vitro stimulation with lymphocytotropic HIV-1 (IIIb and RF), monocytotropic HIV-1 (BaL), Sendai virus, and HSV-1. Active and inactive cell-free preparations of HIV-1 IIIb and cell-associated HIV-1 IIIb, and active cell-free preparations of the other viruses, induced comparable, maximal levels of acid-stable IFN-alpha in PBMC by 18 to 24 h. Negative selection and enrichment experiments indicated that HLA-DR+ "null" cells produced the majority of the IFN-alpha. A positive selection protocol using flow cytometric sorting enriched these HLA-DR+ CD3- CD19- CD16- CD56- CD14- cells to > 95% purity. These were identified as dendritic cells by their phenotype, large size, and veiled and ruffled morphology. The purified dendritic cells produced as much as 60-fold more IFN-alpha compared with purified, HLA-DR+ CD14+ monocytes in response to the viruses. IFN-alpha was not produced by CD3+ T cells or CD56+ NK cells. Purified CD19+ B cells produced a minimal amount of IFN-alpha in response to Sendai virus, and no IFN-alpha in response to the other viruses. Of significance, the dendritic cells expressed CD4 at a density similar to monocytes, and induction of IFN-alpha by HIV-1 could be blocked by HIV-1 gp120 anti-serum or anti-CD4 mAb. We conclude that the production of IFN-alpha constitutes a previously unrecognized major function of blood dendritic cells. This may be a mechanism of innate immunity mediated by dendritic cells against HIV-1 and other viral infections.
Ferbas
J J
JJ
Department of Infectious Diseases and Microbiology, University of Pittsburgh, PA 15261.
Toso
J F
JF
Logar
A J
AJ
Navratil
J S
JS
Rinaldo
C R
CR
D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D003713:Dendritic Cells / Q000276:immunology* / Q000648:ultrastructure; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000096:biosynthesis*; D007700:Kinetics; D016131:Lymphocyte Subsets / Q000276:immunology / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning
D015704:CD4 Antigens; D016898:Interferon-alpha