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Antigen-independent IFN-γ production by human naïve CD4 T cells activated by IL-12 plus IL-18.

Munk RB, Sugiyama K, Ghosh P, Sasaki CY, Rezanka L, Banerjee K, Takahashi H, Sen R, Longo DL - PLoS ONE (2011)

Bottom Line: While p38MAP kinase is involved in transcription, mTOR is involved in message stabilization.We have also shown that NFκB family member, cRel, but not GADD45β and GADD45γ, plays an important role in IL-12 plus IL-18-induced IFN-γ transcription.Thus, the present study suggests that naïve CD4(+) T cells may participate in innate immunity or amplify adaptive immune responses through cytokine-induced antigen-independent cytokine production.

View Article: PubMed Central - PubMed

Affiliation: Lymphocyte Cell Biology Unit, Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.

ABSTRACT
The role of T cells in innate immunity is not well defined. In this report, we show that a subset of human peripheral blood CD4(+) T cells responds to IL-12 plus IL-18, but not to IL-12 or IL-18 alone, by producing IFN-γ in the absence of any antigenic stimulation or cell proliferation. Intracellular staining reveals a small percentage of resting CD4(+) T cells (0.5 to 1.5%) capable of producing IFN-γ in response to IL-12 plus IL-18. Interestingly, both naïve (CD45RA(+)) and memory (CD45RO(+)) CD4(+) populations were responsive to IL-12 plus IL-18 stimulation in producing IFN-γ. The expression of IFN-γinduced by IL-12 and IL-18 is sensitive to rapamycin and SB203580, indicating the possible involvement of mTOR and p38 MAP kinase, respectively, in this synergistic pathway. While p38MAP kinase is involved in transcription, mTOR is involved in message stabilization. We have also shown that NFκB family member, cRel, but not GADD45β and GADD45γ, plays an important role in IL-12 plus IL-18-induced IFN-γ transcription. Thus, the present study suggests that naïve CD4(+) T cells may participate in innate immunity or amplify adaptive immune responses through cytokine-induced antigen-independent cytokine production.

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Related in: MedlinePlus

Synergistic effect of IL-12 plus IL-18 treatment on Stat4 phosphorylation.Human peripheral blood CD4+ T cells were treated with IL-12 and IL-18, either alone or in combination, for different periods of time. Equal amounts of whole cell lysates (35 µg) were analyzed by western blot analysis.
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pone-0018553-g003: Synergistic effect of IL-12 plus IL-18 treatment on Stat4 phosphorylation.Human peripheral blood CD4+ T cells were treated with IL-12 and IL-18, either alone or in combination, for different periods of time. Equal amounts of whole cell lysates (35 µg) were analyzed by western blot analysis.

Mentions: To investigate the signaling synergy between IL-12 and IL-18 stimulation, human peripheral blood CD4+ T cells were stimulated with IL-12 and IL-18, either alone or in combination, for different periods of time. Whole cell lysates were then analyzed for Stat4 phosphorylation by western blot analysis. As shown in Figure 3, the synergy between IL-12 and IL-18 signaling was observed as early as 1 hour, and the synergy was increased with time and persisted for at least 24 hours. These data suggest a possible mechanism underlying the requirement for both IL-12 and IL-18 stimulations in producing IFN-γ.


Antigen-independent IFN-γ production by human naïve CD4 T cells activated by IL-12 plus IL-18.

Munk RB, Sugiyama K, Ghosh P, Sasaki CY, Rezanka L, Banerjee K, Takahashi H, Sen R, Longo DL - PLoS ONE (2011)

Synergistic effect of IL-12 plus IL-18 treatment on Stat4 phosphorylation.Human peripheral blood CD4+ T cells were treated with IL-12 and IL-18, either alone or in combination, for different periods of time. Equal amounts of whole cell lysates (35 µg) were analyzed by western blot analysis.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3091853&req=5

pone-0018553-g003: Synergistic effect of IL-12 plus IL-18 treatment on Stat4 phosphorylation.Human peripheral blood CD4+ T cells were treated with IL-12 and IL-18, either alone or in combination, for different periods of time. Equal amounts of whole cell lysates (35 µg) were analyzed by western blot analysis.
Mentions: To investigate the signaling synergy between IL-12 and IL-18 stimulation, human peripheral blood CD4+ T cells were stimulated with IL-12 and IL-18, either alone or in combination, for different periods of time. Whole cell lysates were then analyzed for Stat4 phosphorylation by western blot analysis. As shown in Figure 3, the synergy between IL-12 and IL-18 signaling was observed as early as 1 hour, and the synergy was increased with time and persisted for at least 24 hours. These data suggest a possible mechanism underlying the requirement for both IL-12 and IL-18 stimulations in producing IFN-γ.

Bottom Line: While p38MAP kinase is involved in transcription, mTOR is involved in message stabilization.We have also shown that NFκB family member, cRel, but not GADD45β and GADD45γ, plays an important role in IL-12 plus IL-18-induced IFN-γ transcription.Thus, the present study suggests that naïve CD4(+) T cells may participate in innate immunity or amplify adaptive immune responses through cytokine-induced antigen-independent cytokine production.

View Article: PubMed Central - PubMed

Affiliation: Lymphocyte Cell Biology Unit, Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.

ABSTRACT
The role of T cells in innate immunity is not well defined. In this report, we show that a subset of human peripheral blood CD4(+) T cells responds to IL-12 plus IL-18, but not to IL-12 or IL-18 alone, by producing IFN-γ in the absence of any antigenic stimulation or cell proliferation. Intracellular staining reveals a small percentage of resting CD4(+) T cells (0.5 to 1.5%) capable of producing IFN-γ in response to IL-12 plus IL-18. Interestingly, both naïve (CD45RA(+)) and memory (CD45RO(+)) CD4(+) populations were responsive to IL-12 plus IL-18 stimulation in producing IFN-γ. The expression of IFN-γinduced by IL-12 and IL-18 is sensitive to rapamycin and SB203580, indicating the possible involvement of mTOR and p38 MAP kinase, respectively, in this synergistic pathway. While p38MAP kinase is involved in transcription, mTOR is involved in message stabilization. We have also shown that NFκB family member, cRel, but not GADD45β and GADD45γ, plays an important role in IL-12 plus IL-18-induced IFN-γ transcription. Thus, the present study suggests that naïve CD4(+) T cells may participate in innate immunity or amplify adaptive immune responses through cytokine-induced antigen-independent cytokine production.

Show MeSH
Related in: MedlinePlus