Attenuation of Th1 response in decoy receptor 3 transgenic mice.
The soluble decoy receptor 3 (DcR3) is a member of the TNFR superfamily. Because DcR3 is up-regulated in tumor tissues and is detectable in the sera of cancer patients, it is regarded as an immunosuppressor to down-regulate immune responses. To understand the function of DcR3 in vivo, we generated transgenic mice overexpressing DcR3 systemically. In comparison with HNT-TCR (HNT) transgenic mice, up-regulation of IL-4 and IL-10 and down-regulation of IFN-gamma, IL-12, and TNF-alpha were observed in the influenza hemagglutinin(126-138) peptide-stimulated splenocytes of HNT-DcR3 double-transgenic mice. When infected with Listeria monocytogenes, DcR3 transgenic mice show attenuated expression of IFN-gamma as well as increased susceptibility to infection. The Th2 cell-biased phenotype in DcR3 transgenic mice is attributed to decreased IL-2 secretion by T cells, resulting in the suppression of IL-2 dependent CD4(+) T cell proliferation. This suggests that DcR3 might help tumor growth by attenuating the Th1 response and suppressing cell-mediated immunity.
Hsu
Tsui-Ling
TL
Institute of Microbiology and Immunology, National Yang-Ming University, Shih-Pai, Taipei, Taiwan.
Wu
Ying-Yu
YY
Chang
Yung-Chi
YC
Yang
Chih-Ya
CY
Lai
Ming-Zong
MZ
Su
Wenlynn B
WB
Hsieh
Shie-Liang
SL
D000276:Adjuvants, Immunologic / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D053222:Fas Ligand Protein; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology; D048069:Tumor Necrosis Factors / Q000378:metabolism
D000276:Adjuvants, Immunologic; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human; C505914:TNFSF14 protein, human; C117026:TNFSF15 protein, human; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors