Morphological and Functional Differences Between HLA-DR+ Peripheral Blood Dendritic Cells and HLA-DR+ FN-Alpha Producing Cells

Self Cite

325

278

We report in this study the generation of a novel rat mAb that recognizes mouse plasmacytoid dendritic cells (pDC). This Ab, named 120G8, stains a small subset of CD11clow spleen cell with high specificity. This population produces high amounts of IFN-α upon in vitro viral stimulation. Both ex vivo- and in vitro-derived 120G8+ cells display a phenotype identical with that of the previously described mouse pDC (B220highLy6ChighGr1lowCD11b−CD11clow). Mice treated with 120G8 mAb are depleted of B220highLy6ChighCD11clow cells and have a much-reduced ability to produce IFN-α in response to in vivo CpG stimulation. The mAb 120G8 stains all and only B220highLy6ChighCD11clow pDC in all lymphoid organs. Immunohistochemical studies performed with this mAb indicate that pDC are located in the T cell area of spleen, lymph nodes, and Peyer’s patches. Although the Ag recognized by 120G8 is not yet known, we show that its expression is up-regulated by type I IFN on B cells and DC. Using this mAb in immunofluorescence studies demonstrates strain- and organ-specific differences in the frequency of pDC and other DC subsets. 129Sv mice have a much higher frequency of pDC, together with a lower frequency of conventional CD8α+CD11chigh DC, compared with C57BL/6 mice, both in spleen and blood. The higher ability of 129Sv mice to produce IFN-α in vivo is related to a higher number of pDC, but also to a higher ability of pDC from 129Sv mice to produce IFN-α in vitro in response to viral stimulation.

Section: Endritic Cells (Dc)mentioning

confidence: 99%

Mouse Strain Differences in Plasmacytoid Dendritic Cell Frequency and Function Revealed by a Novel Monoclonal Antibody

Asselin‐Paturel¹,

Brizard²,

Pin³

et al. 2003

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325

278

“…MDC, also referred to as DC1 or APC type 1 (APC1), express CD11c and CD1c Ags and are associated with Ag uptake, T cell activation, dendritic morphology, stimulation of MLRs, and ability to secrete IL-12 in response to bacterial stimuli (9 -11). PDC, also referred to as lymphoid DC, DC2, APC2, or IFN-␣-producing cells, express CD123, BDCA-2, and BDCA-4 Ags and are characterized by a lymphoid morphology, modest Agpresenting potential, and high virus-induced IFN-␣ secretion (7,9,10,12,13). Dysfunction and potential loss of DC subsets in HIV-1 infection could be associated with decreased T cell activation (Agspecific or allogeneic responses) and secretion of type 1 cytokines (e.g., IL-12, IL-15, and IFN-␣) that may be in part responsible for the patients' increased susceptibility to O.I.…”

Section: H Uman Immunodeficiency Virus Infection Is Associatedmentioning

confidence: 99%

Persistent Decreases in Blood Plasmacytoid Dendritic Cell Number and Function Despite Effective Highly Active Antiretroviral Therapy and Increased Blood Myeloid Dendritic Cells in HIV-Infected Individuals

Chehimi¹,

Campbell

Azzoni³

et al. 2002

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312

236

Dendritic cells (DC) have an instrumental role in the activation and function of both innate and adaptive immune responses. In humans, at least two distinct DC subsets have been characterized based on phenotypic markers: the myeloid DC (MDC) and the plasmacytoid DC (PDC). Both subsets are critical producers of cytokines (IL-12 for MDC and type I/II IFNs for PDC) and are functionally different. We show in this study that HIV+ individuals have a significant decrease in the number of the Lin−HLA-DR+CD123+ and BDCA-2+ PDC compared with uninfected donors (p = 0.0001). HIV+ individuals also have a sustained impairment in viral-induced IFN-α production (p < 0.0001). The decrease of the PDC subsets did not correlate with CD4 count or viral load and was not reversed in subjects under virally suppressive treatment, suggesting an irreversible change after infection. By contrast, the absolute number and median frequency of MDC in HIV-infected individuals were similar to those observed in uninfected controls, while a significant decrease was present in subjects with >5000 HIV-1 copies/ml. The inverse association with viral load of the MDC number, but not of IFN-α secretion or the number of PDC, suggests a role for MDC in viral control. Our data suggest that DC subsets are differentially reconstituted during the immune recovery associated with antiviral therapy. The persistent impairment of certain DC subsets may result in a sustained defect in DC-mediated innate immune functions despite an effective treatment regimen.

“…Immature mDCs are characterized by effective Ag uptake. Following maturation, they acquire dendritic morphology, potent Ag presentation capacity, and marked ability to stimulate Ag-specific T cell responses (2)(3)(4).…”

Section: Endritic Cells (Dcs)mentioning

confidence: 99%

“…With appropriate stimuli, they can migrate directly from the peripheral blood to lymph nodes and lymphoid organs. PDCs are characterized by strong Ag-presenting potential, lymphoid morphology, and high virus-induced and CD40-mediated IFN-␣ secretion (2,3,5,6). Thus, mDCs, and particularly PDCs, are instrumental in antiviral innate immunity and shaping Th1 adaptive immune responses to viral pathogens.…”

Section: Pdcs Are Cd123mentioning

confidence: 99%

A Blunted Blood Plasmacytoid Dendritic Cell Response to an Acute Systemic Viral Infection Is Associated with Increased Disease Severity

Pichyangkul

Endy

Kalayanarooj

et al. 2003

104

At least two distinct human dendritic cell (DC) subsets are produced in the bone marrow and circulate in the peripheral blood-precursor myeloid DCs (pre-mDCs) and plasmacytoid DCs (PDCs). Both lineages of DCs are instrumental in antiviral innate immunity and shaping Th1 adaptive immune responses. PDCs are the most potent IFN-α-producing cells to viral pathogens. Dengue, an acute flavivirus disease, provides a model to study DC responses to a self-limited human viral infection. We analyzed circulating DC subsets in a prospective study of children with dengue across a broad range of illness severities: healthy controls; mild, nondengue, presumed viral infections; moderately ill dengue fever; and, the most severe form of illness, dengue hemorrhagic fever. We also examined PDC responses in monkeys with asymptomatic dengue viremia and to dengue virus exposure in vitro. The absolute number and frequency of circulating pre-mDCs early in acute viral illness decreased as illness severity increased. Depressed pre-mDC blood levels appeared to be part of the typical innate immune response to acute viral infection. The frequency of circulating PDCs trended upward and the absolute number of circulating PDCs remained stable early in moderately ill children with dengue fever, mild other, nondengue, febrile illness, and monkeys with asymptomatic dengue viremia. However, there was an early decrease in circulating PDC levels in children who subsequently developed dengue hemorrhagic fever. A blunted blood PDC response to dengue virus infection was associated with higher viremia levels, and was part of an altered innate immune response and pathogenetic cascade leading to severe disease.