9782125

pubmed:Citation

8

Interleukin (IL)-18 induces interferon (IFN)-gamma synthesis and synergizes with IL-12 in T helper type 1 (Th1) but not Th2 cell development. We report here that IL-18 receptor (IL-18R) is selectively expressed on murine Th1 but not Th2 cells. IL-18R mRNA was expressed constitutively and consistently in long-term cultured clones, as well as on newly polarized Th1 but not Th2 cells. IL-18 sustained the expression of IL-12Rbeta2 mRNA, indicating that IL-18R transmits signals that maintain Th1 development through the IL-12R complex. In turn, IL-12 upregulated IL-18R mRNA. Antibody against an IL-18R-derived peptide bound Th1 but not Th2 clones. It also labeled polarized Th1 but not Th2 cells derived from naive ovalbumin-T cell antigen receptor-alphabeta transgenic mice (D011.10). Anti-IL-18R antibody inhibited IL-18- induced IFN-gamma production by Th1 clones in vitro. In vivo, anti-IL-18R antibody reduced local inflammation and lipopolysaccharide-induced mortality in mice. This was accompanied by shifting the balance from Th1 to Th2 responses, manifest as decreased IFN-gamma and proinflammatory cytokine production and increased IL-4 and IL-5 synthesis. Therefore, these data provide a direct mechanism for the selective effect of IL-18 on Th1 but not Th2 cells. They also show that the synergistic effect of IL-12 and IL-18 on Th1 development may be due to the reciprocal upregulation of their receptors. Furthermore, IL-18R is a cell surface marker distinguishing Th1 from Th2 cells and may be a therapeutic target.

http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-1590992, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-2117636, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-2125367, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-2147202, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-2419430, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-2532153, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-4544249, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-7477296, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-7514136, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-7595206, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-7821763, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-8011282, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-8078923, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-8237615, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-8584935, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-8626725, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-8666798, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-8808632, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-8985251, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-9029088, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-9120387, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-9120388, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-9143690, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-9302298, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-9325300, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-9354477, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-9419219, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-9435236, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-9450746, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-9480988, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-9492992, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-9500790, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-9514903, http://linkedlifedata.com/resource/pubmed/commentcorrection/9782125-9529155

http://linkedlifedata.com/resource/pubmed/journal/2985109R

http://linkedlifedata.com/resource/pubmed/chemical/Il18r1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18 Receptor alpha..., http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-18

Oct

pubmed-author:CarterR WRW, pubmed-author:ChanW LWL, pubmed-author:HunterDD, pubmed-author:LeungB PBP, pubmed-author:LiewF YFY, pubmed-author:McInnesI BIB, pubmed-author:RobinsonJ HJH, pubmed-author:SchulzKK, pubmed-author:XuDD

19

NLM

1485-92

pubmed-meshheading:9782125-Animals, pubmed-meshheading:9782125-Cell Line, pubmed-meshheading:9782125-Inflammation, pubmed-meshheading:9782125-Interferon-gamma, pubmed-meshheading:9782125-Interleukin-12, pubmed-meshheading:9782125-Interleukin-18, pubmed-meshheading:9782125-Interleukin-18 Receptor alpha Subunit, pubmed-meshheading:9782125-Lipopolysaccharides, pubmed-meshheading:9782125-Mice, pubmed-meshheading:9782125-Mice, Inbred BALB C, pubmed-meshheading:9782125-Mice, Inbred CBA, pubmed-meshheading:9782125-Receptors, Interleukin, pubmed-meshheading:9782125-Receptors, Interleukin-18, pubmed-meshheading:9782125-Shock, Septic, pubmed-meshheading:9782125-Th1 Cells, pubmed-meshheading:9782125-Th2 Cells

Selective expression and functions of interleukin 18 receptor on T helper (Th) type 1 but not Th2 cells.

Journal Article, Research Support, Non-U.S. Gov't