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Mouse plasmacytoid cells: long-lived cells, heterogeneous in surface phenotype and function, that differentiate into CD8(+) dendritic cells only after microbial stimulus.

O'Keeffe M, Hochrein H, Vremec D, Caminschi I, Miller JL, Anders EM, Wu L, Lahoud MH, Henri S, Scott B, Hertzog P, Tatarczuch L, Shortman K - J. Exp. Med. (2002)

Bottom Line: Similar experiments indicate that p-preDCs are normally long lived and are not the precursors of the short-lived steady-state conventional DCs.Hence as well as activating preexistant DCs, microbial infection induces a wave of production of a new DC subtype.The functional implications of this shift in the DC network remain to be determined.

View Article: PubMed Central - PubMed

Affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia. okeefe@wehi.edu.au

ABSTRACT
The CD45RA(hi)CD11c(int) plasmacytoid predendritic cells (p-preDCs) of mouse lymphoid organs, when stimulated in culture with CpG or influenza virus, produce large amounts of type I interferons and transform without division into CD8(+)CD205(-) DCs. P-preDCs express CIRE, the murine equivalent of DC-specific intercellular adhesion molecule 3 grabbing nonintegrin (DC-SIGN). P-preDCs are divisible by CD4 expression into two subgroups differing in turnover rate and in response to Staphylococcus aureus. The kinetics of bromodeoxyuridine labeling and the results of transfer to normal recipient mice indicate that CD4(-) p-preDCs are the immediate precursors of CD4(+) p-preDCs. Similar experiments indicate that p-preDCs are normally long lived and are not the precursors of the short-lived steady-state conventional DCs. However, in line with the culture studies on transfer to influenza virus-stimulated mice the p-preDCs transform into CD8(+)CD205(-) DCs, distinct from conventional CD8(+)CD205(+) DCs. Hence as well as activating preexistant DCs, microbial infection induces a wave of production of a new DC subtype. The functional implications of this shift in the DC network remain to be determined.

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Activated spleen p-preDC produce IFN-α, IL-12, and IL-6. (A) Bioassay for the production of type I IFN from p-preDCs cultured for 14 h with IL-3 and GM-CSF alone, or with additional cytokines and stimulants. The “IL-12 inducing cytokines” were IL-3, GM-CSF, rat IFN-γ, and IL-4. The values shown represent the means of duplicate samples; similar results were obtained in three separate experiments. Culturing of p-preDCs for up to 80 h yielded similar supernatant levels of type I IFN. The production of type I IFN from p-preDCs stimulated with BPL-Guangdong and live Guangdong virus was also shown by bioassay in a single experiment; the levels being higher than with CpG. (B) ELISA for the production of IFN-α from p-preDCs cultured for 14 h in the presence of IL-3 and GM-CSF together with the stimulants shown. The results shown were similar to those obtained in three separate experiments for LPS and BPL-Guangdong and in five separate experiments for IL-3 and GM-CSF with or without CpG. The values shown are the means of duplicate samples and the error bars represent the range. (C) ELISA for the production of IL-12 p70 from spleen p-preDCs cultured for 14 h with IL-3 and GM-CSF alone, or together with additional cytokines and stimulants. IL-12 inducing cytokines were IL-3, GM-CSF, rat IFN-γ, and IL-4. The values shown are the means of duplicate samples and the error bars represent the range; similar results were obtained in three separate experiments. (D) ELISA for the production of IL-6 from spleen p-preDCs cultured for 14 h with IL-3 and GM-CSF alone, or together with CpG. The values shown are the means of duplicate samples and the error bars represent the range; similar results were obtained in three separate experiments.
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fig3: Activated spleen p-preDC produce IFN-α, IL-12, and IL-6. (A) Bioassay for the production of type I IFN from p-preDCs cultured for 14 h with IL-3 and GM-CSF alone, or with additional cytokines and stimulants. The “IL-12 inducing cytokines” were IL-3, GM-CSF, rat IFN-γ, and IL-4. The values shown represent the means of duplicate samples; similar results were obtained in three separate experiments. Culturing of p-preDCs for up to 80 h yielded similar supernatant levels of type I IFN. The production of type I IFN from p-preDCs stimulated with BPL-Guangdong and live Guangdong virus was also shown by bioassay in a single experiment; the levels being higher than with CpG. (B) ELISA for the production of IFN-α from p-preDCs cultured for 14 h in the presence of IL-3 and GM-CSF together with the stimulants shown. The results shown were similar to those obtained in three separate experiments for LPS and BPL-Guangdong and in five separate experiments for IL-3 and GM-CSF with or without CpG. The values shown are the means of duplicate samples and the error bars represent the range. (C) ELISA for the production of IL-12 p70 from spleen p-preDCs cultured for 14 h with IL-3 and GM-CSF alone, or together with additional cytokines and stimulants. IL-12 inducing cytokines were IL-3, GM-CSF, rat IFN-γ, and IL-4. The values shown are the means of duplicate samples and the error bars represent the range; similar results were obtained in three separate experiments. (D) ELISA for the production of IL-6 from spleen p-preDCs cultured for 14 h with IL-3 and GM-CSF alone, or together with CpG. The values shown are the means of duplicate samples and the error bars represent the range; similar results were obtained in three separate experiments.

Mentions: Results are representative of 2–10 experiments. ND, not done. The absolute values of cytokines produced are shown in Fig. 3 and Fig. 6 C.


Mouse plasmacytoid cells: long-lived cells, heterogeneous in surface phenotype and function, that differentiate into CD8(+) dendritic cells only after microbial stimulus.

O'Keeffe M, Hochrein H, Vremec D, Caminschi I, Miller JL, Anders EM, Wu L, Lahoud MH, Henri S, Scott B, Hertzog P, Tatarczuch L, Shortman K - J. Exp. Med. (2002)

Activated spleen p-preDC produce IFN-α, IL-12, and IL-6. (A) Bioassay for the production of type I IFN from p-preDCs cultured for 14 h with IL-3 and GM-CSF alone, or with additional cytokines and stimulants. The “IL-12 inducing cytokines” were IL-3, GM-CSF, rat IFN-γ, and IL-4. The values shown represent the means of duplicate samples; similar results were obtained in three separate experiments. Culturing of p-preDCs for up to 80 h yielded similar supernatant levels of type I IFN. The production of type I IFN from p-preDCs stimulated with BPL-Guangdong and live Guangdong virus was also shown by bioassay in a single experiment; the levels being higher than with CpG. (B) ELISA for the production of IFN-α from p-preDCs cultured for 14 h in the presence of IL-3 and GM-CSF together with the stimulants shown. The results shown were similar to those obtained in three separate experiments for LPS and BPL-Guangdong and in five separate experiments for IL-3 and GM-CSF with or without CpG. The values shown are the means of duplicate samples and the error bars represent the range. (C) ELISA for the production of IL-12 p70 from spleen p-preDCs cultured for 14 h with IL-3 and GM-CSF alone, or together with additional cytokines and stimulants. IL-12 inducing cytokines were IL-3, GM-CSF, rat IFN-γ, and IL-4. The values shown are the means of duplicate samples and the error bars represent the range; similar results were obtained in three separate experiments. (D) ELISA for the production of IL-6 from spleen p-preDCs cultured for 14 h with IL-3 and GM-CSF alone, or together with CpG. The values shown are the means of duplicate samples and the error bars represent the range; similar results were obtained in three separate experiments.
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Related In: Results  -  Collection

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fig3: Activated spleen p-preDC produce IFN-α, IL-12, and IL-6. (A) Bioassay for the production of type I IFN from p-preDCs cultured for 14 h with IL-3 and GM-CSF alone, or with additional cytokines and stimulants. The “IL-12 inducing cytokines” were IL-3, GM-CSF, rat IFN-γ, and IL-4. The values shown represent the means of duplicate samples; similar results were obtained in three separate experiments. Culturing of p-preDCs for up to 80 h yielded similar supernatant levels of type I IFN. The production of type I IFN from p-preDCs stimulated with BPL-Guangdong and live Guangdong virus was also shown by bioassay in a single experiment; the levels being higher than with CpG. (B) ELISA for the production of IFN-α from p-preDCs cultured for 14 h in the presence of IL-3 and GM-CSF together with the stimulants shown. The results shown were similar to those obtained in three separate experiments for LPS and BPL-Guangdong and in five separate experiments for IL-3 and GM-CSF with or without CpG. The values shown are the means of duplicate samples and the error bars represent the range. (C) ELISA for the production of IL-12 p70 from spleen p-preDCs cultured for 14 h with IL-3 and GM-CSF alone, or together with additional cytokines and stimulants. IL-12 inducing cytokines were IL-3, GM-CSF, rat IFN-γ, and IL-4. The values shown are the means of duplicate samples and the error bars represent the range; similar results were obtained in three separate experiments. (D) ELISA for the production of IL-6 from spleen p-preDCs cultured for 14 h with IL-3 and GM-CSF alone, or together with CpG. The values shown are the means of duplicate samples and the error bars represent the range; similar results were obtained in three separate experiments.
Mentions: Results are representative of 2–10 experiments. ND, not done. The absolute values of cytokines produced are shown in Fig. 3 and Fig. 6 C.

Bottom Line: Similar experiments indicate that p-preDCs are normally long lived and are not the precursors of the short-lived steady-state conventional DCs.Hence as well as activating preexistant DCs, microbial infection induces a wave of production of a new DC subtype.The functional implications of this shift in the DC network remain to be determined.

View Article: PubMed Central - PubMed

Affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia. okeefe@wehi.edu.au

ABSTRACT
The CD45RA(hi)CD11c(int) plasmacytoid predendritic cells (p-preDCs) of mouse lymphoid organs, when stimulated in culture with CpG or influenza virus, produce large amounts of type I interferons and transform without division into CD8(+)CD205(-) DCs. P-preDCs express CIRE, the murine equivalent of DC-specific intercellular adhesion molecule 3 grabbing nonintegrin (DC-SIGN). P-preDCs are divisible by CD4 expression into two subgroups differing in turnover rate and in response to Staphylococcus aureus. The kinetics of bromodeoxyuridine labeling and the results of transfer to normal recipient mice indicate that CD4(-) p-preDCs are the immediate precursors of CD4(+) p-preDCs. Similar experiments indicate that p-preDCs are normally long lived and are not the precursors of the short-lived steady-state conventional DCs. However, in line with the culture studies on transfer to influenza virus-stimulated mice the p-preDCs transform into CD8(+)CD205(-) DCs, distinct from conventional CD8(+)CD205(+) DCs. Hence as well as activating preexistant DCs, microbial infection induces a wave of production of a new DC subtype. The functional implications of this shift in the DC network remain to be determined.

Show MeSH
Related in: MedlinePlus