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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Bibliographic Details
Published in:	PloS one Vol. 6; no. 5; p. e18553
Main Authors:	Munk, Rachel B., Sugiyama, Katsuki, Ghosh, Paritosh, Sasaki, Carl Y., Rezanka, Louis, Banerjee, Kasturi, Takahashi, Hidenori, Sen, Ranjan, Longo, Dan L.
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 10.05.2011 Public Library of Science (PLoS)
Subjects:	Adaptive immunity Animals Antigens Antigens, Differentiation - metabolism Biology CD4 antigen CD4-Positive T-Lymphocytes - drug effects CD4-Positive T-Lymphocytes - metabolism CD45RA antigen Cell proliferation Cells, Cultured Humans Imidazoles - pharmacology Immune response Immunity Innate immunity Interferon Interferon-gamma - genetics Interferon-gamma - metabolism Interleukin 12 Interleukin 18 Interleukin-12 - pharmacology Interleukin-18 - pharmacology Intracellular Signaling Peptides and Proteins - metabolism Kinases Laboratories Listeria monocytogenes Lymphocytes Lymphocytes T Male MAP kinase Mice NF-κB protein p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors p38 Mitogen-Activated Protein Kinases - metabolism Peripheral blood Phosphorylation - drug effects Polymerase Chain Reaction Pyridines - pharmacology Rapamycin Sirolimus - pharmacology STAT4 Transcription Factor - metabolism Stimulation T cell receptors TOR protein TOR Serine-Threonine Kinases - antagonists & inhibitors TOR Serine-Threonine Kinases - metabolism Transcription γ-Interferon United States > US Maryland Baltimore Maryland
ISSN:	1932-6203, 1932-6203
Online Access:	Get full text
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: RM DLL. Performed the experiments: RM KS PG CYS LR KB. Analyzed the data: RM PG LR RS DLL HT. Wrote the paper: KS PG DLL.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0018553