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

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. Intracellula...

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Main Authors: Rachel B Munk, Katsuki Sugiyama, Paritosh Ghosh, Carl Y Sasaki, Louis Rezanka, Kasturi Banerjee, Hidenori Takahashi, Ranjan Sen, Dan L Longo
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-05-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3091853?pdf=render
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author Rachel B Munk
Katsuki Sugiyama
Paritosh Ghosh
Carl Y Sasaki
Louis Rezanka
Kasturi Banerjee
Hidenori Takahashi
Ranjan Sen
Dan L Longo
author_facet Rachel B Munk
Katsuki Sugiyama
Paritosh Ghosh
Carl Y Sasaki
Louis Rezanka
Kasturi Banerjee
Hidenori Takahashi
Ranjan Sen
Dan L Longo
author_sort Rachel B Munk
collection DOAJ
description 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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spelling doaj.art-e66d1bc13d5a4f439759c52e841326412022-12-22T02:05:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-05-0165e1855310.1371/journal.pone.0018553Antigen-independent IFN-γ production by human naïve CD4 T cells activated by IL-12 plus IL-18.Rachel B MunkKatsuki SugiyamaParitosh GhoshCarl Y SasakiLouis RezankaKasturi BanerjeeHidenori TakahashiRanjan SenDan L LongoThe 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.http://europepmc.org/articles/PMC3091853?pdf=render
spellingShingle Rachel B Munk
Katsuki Sugiyama
Paritosh Ghosh
Carl Y Sasaki
Louis Rezanka
Kasturi Banerjee
Hidenori Takahashi
Ranjan Sen
Dan L Longo
Antigen-independent IFN-γ production by human naïve CD4 T cells activated by IL-12 plus IL-18.
PLoS ONE
title Antigen-independent IFN-γ production by human naïve CD4 T cells activated by IL-12 plus IL-18.
title_full Antigen-independent IFN-γ production by human naïve CD4 T cells activated by IL-12 plus IL-18.
title_fullStr Antigen-independent IFN-γ production by human naïve CD4 T cells activated by IL-12 plus IL-18.
title_full_unstemmed Antigen-independent IFN-γ production by human naïve CD4 T cells activated by IL-12 plus IL-18.
title_short Antigen-independent IFN-γ production by human naïve CD4 T cells activated by IL-12 plus IL-18.
title_sort antigen independent ifn γ production by human naive cd4 t cells activated by il 12 plus il 18
url http://europepmc.org/articles/PMC3091853?pdf=render
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