Functional deficiencies in two distinct interferon α-producing cell populations in peripheral blood mononuclear cells from human immunodeficiency virus seropositive patients

Abstract

Two populations of IFN-alpha producing cells (IPC) were examined to determine whether they are coordinately dysregulated in human immunodeficiency virus (HIV) disease. IFN-alpha produced in response to herpes simplex virus (HSV) and Sendai virus (SV) was measured and the frequencies of the IPC were obtained by ELISpot assay. IPC that respond to HSV (natural IFN-alpha producing cells) and those responding to SV (predominantly monocytes) were present, on average, at 7.6 and 138 per 10(4) PBMC in healthy controls, respectively. More patients had a reduced IFN-alpha response to HSV than to SV, and individual patients did not show a decreased response to SV without a decreased response to HSV. Neither IPC function was correlated with CD4+ cell levels. We conclude that the defects in IFN-alpha production in these two cell populations arise independently, possibly due to differences in susceptibility to HIV infection or molecular regulation.

Characterization of Virus-Responsive Plasmacytoid Dendritic Cells in the Rhesus Macaque

“…Human PDC constitute Ͻ1% of PBMC, making them difficult to isolate and study in large numbers. However, human PDC can be identified by using flow cytometry, allowing us to gate in on the small population of cells for both phenotypic and functional analysis (13). Human PDC have been characterized as cells that are lineage marker negative, HLA-DR ϩ , CD123 bright , and CD11c Ϫ (Fig.…”

“…The markedly lower frequency of SV-responsive IPC in monkeys compared to humans may reflect limitations to the ELISPOT assay. SV is known to induce both PDC and monocytes to produce IFN-␣, with the monocytes expressing 5-to 10-fold lower expression of IFN-␣ on a per-cell basis than the PDC (13,20). In the ELISPOT, this is seen by a mixture of small (monocyte-derived) and large (PDC-derived) spots.…”

“…ELISPOT assays for detection of IFN-␣-producing cells were carried out as previously described (13). Briefly, PBMC (10 6 /ml) were either mock stimulated (placed in the incubator with no virus) or stimulated for 6 h with HSV-1 at an multiplicity of infection of 1.…”

Production of Interleukin‐4, Interferon (IFN)‐γ and IFN‐α in Human Immunodeficiency Virus‐1 Infection: An Imbalance of Type 1 and Type 2 Cytokines may Reduce the Synthesis of IFN‐α

“…In other studies, the defect in ex vivo production of IFN-a in HIV-1-infected patients has been described but its mechanism remains unclear [12][13][14][15][16][17]. This is the first report of an association between the profile of T-cell-derived cytokines and the production of IFN-a in HIV-1 infection.…”

A correlation of measles specific antibodies and the number of plasmacytoid dendritic cells is observed after measles vaccination in 9 month old infants

“…While mDCs are present in virtually all organs 21 and perform virtually all tasks involved in triggering immune response, 21,22 pDCs constitute a unique cell population comprising only 0.2-0.8% of all peripheral blood mononuclear cells (PBMCs). 23,24 The pDCs express surface molecules CD4, CD45RA, a-chain of IL-3 and Major Histocompatibility Complex (MHC II) molecules (HLA-DRII), but lack typical markers of other common cell lineages, CD3, CD11c, CD11b, CD14, CD16, CD19 and CD56. Additionally, the pDCs express specific markers such as CD303 (BDCA-2-type II transmembrane glycoprotein-C-type lectin) and CD304 (BDCA-4-neuropilin 1).…”