Journal ArticleDOI
Interleukin-12 and the regulation of innate resistance and adaptive immunity
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TLDR
The understanding of the relative roles of IL-12 and other factors in TH1-type maturation of both CD4+ and CD8+ T cells is discussed here, including the participation in this process ofIL-23 and IL-27, two recently discovered members of the new family of heterodimeric cytokines.Abstract:
Interleukin-12 (IL-12) is a heterodimeric pro-inflammatory cytokine that induces the production of interferon-gamma (IFN-gamma), favours the differentiation of T helper 1 (T(H)1) cells and forms a link between innate resistance and adaptive immunity. Dendritic cells (DCs) and phagocytes produce IL-12 in response to pathogens during infection. Production of IL-12 is dependent on differential mechanisms of regulation of expression of the genes encoding IL-12, patterns of Toll-like receptor (TLR) expression and cross-regulation between the different DC subsets, involving cytokines such as IL-10 and type I IFN. Recent data, however, argue against an absolute requirement for IL-12 for T(H)1 responses. Our understanding of the relative roles of IL-12 and other factors in T(H)1-type maturation of both CD4+ and CD8+ T cells is discussed here, including the participation in this process of IL-23 and IL-27, two recently discovered members of the new family of heterodimeric cytokines.read more
Citations
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References
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Journal ArticleDOI
TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties.
Tim R. Mosmann,R L Coffman +1 more
TL;DR: Two types of cloned helper T cells are described, defined primarily by differences in the pattern of lymphokines ynthesized, and the different functions of the two types of cells and their lymphokine synthesis are discussed.
Journal ArticleDOI
A novel transcription factor, T-bet, directs Th1 lineage commitment.
Susanne J. Szabo,Sean T Kim,Gina L. Costa,Xiankui Zhang,C. Garrison Fathman,Laurie H. Glimcher +5 more
TL;DR: T-bet initiates Th1 lineage development from naive Thp cells both by activating Th1 genetic programs and by repressing the opposing Th2 programs, as evidenced by the simultaneous induction of IFNgamma and repression of IL-4 and IL-5.
Journal ArticleDOI
Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages
Chyi-Song Hsieh,Steven E. Macatonia,Catherine S. Tripp,Stanley F. Wolf,Anne O'Garra,Kenneth M. Murphy +5 more
TL;DR: This regulatory pathway may have evolved to enable innate immune cells, through interactions with microbial pathogens, to direct development of specific immunity toward the appropriate TH1 phenotype.
Journal ArticleDOI
Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12.
Birgit Oppmann,Robin Lesley,Bianca Blom,Jackie C. Timans,Yuming Xu,Brisdell Hunte,Felix Vega,Nancy Yu,Jing Wang,Komal Singh,Francesca Zonin,Elena Vaisberg,Tatyana Churakova,Man ru Liu,Daniel M. Gorman,Janet Wagner,Sandra Zurawski,Yong-Jun Liu,John S. Abrams,Kevin W. Moore,Donna Rennick,Rene de Waal-Malefyt,Charles H. Hannum,J. Fernando Bazan,Robert A. Kastelein +24 more
TL;DR: Human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells and induces strong proliferation of mouse memory T cells.
Journal ArticleDOI
Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation.
TL;DR: It is found that ligation of CD40 by CD40L triggers the production of extremely high levels of bioactive IL-12, which is the most potent stimulus in upregulating the expression of ICAM-1, CD80, and CD86 molecules on DCs.
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