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10.1073/pnas.0611139104 http://scihub22266oqcxt.onion/10.1073/pnas.0611139104 17372206!1851602!17372206     free     free     free Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Proc+Natl+Acad+Sci+U+S+A 2007 ; 104 (14): 5977-82 Nephropedia Template TP {{tp|p=17372206|t=2007. Normal development and function of invariant natural killer T cells in mice with isoglobotrihexosylceramide (iGb3) deficiency |pdf=|usr=}}{{17372206}} gab.com Text Normal development and function of invariant natural killer T cells in mice with isoglobotrihexosylceramide (iGb3) deficiency JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=17372206 #FOAvip CD1d-restricted natural killer T (NKT) cells, expressing the invariant T cell antigen receptor (TCR) chain encoded by Valpha14-Jalpha18 gene segments in mice and Valpha24-Jalpha18 in humans [invariant NKT (iNKT) cells], contribute to immunoregulatory processes, such as tolerance, host defense, and tumor surveillance. iNKT cells are positively selected in the thymus by CD1d molecules expressed by CD4(+)/CD8(+) cortical thymocytes. However, the identity of the endogenous lipid(s) responsible for positive selection of iNKT cells remains unclear. One candidate lipid proposed to play a role in positive selection is isoglobotrihexosylceramide (iGb3). However, no direct evidence for its physiological role has been provided. Therefore, to directly investigate the role of iGb3 in iNKT cell selection, we have generated mice deficient in iGb3 synthase [iGb3S, also known as alpha1-3galactosyltransferase 2 (A3galt2)]. These mice developed, grew, and reproduced normally and exhibited no overt behavioral abnormalities. Consistent with the notion that iGb3 is synthesized only by iGb3S, lack of iGb3 in the dorsal root ganglia of iGb3S-deficient mice (iGb3S(-/-)), as compared with iGb3S(+/-) mice, was confirmed. iGb3S(-/-) mice showed normal numbers of iNKT cells in the thymus, spleen, and liver with selected TCR Vbeta chains identical to controls. Upon administration of alpha-galactosylceramide, activation of iNKT and dendritic cells was similar in iGb3S(-/-) and iGb3S(+/-) mice, as measured by up-regulation of CD69 as well as intracellular IL-4 and IFN-gamma in iNKT cells, up-regulation of CD86 on dendritic cells, and rise in serum concentrations of IL-4, IL-6, IL-10, IL-12p70, IFN-gamma, TNF-alpha, and Ccl2/MCP-1. Our results strongly suggest that iGb3 is unlikely to be an endogenous CD1d lipid ligand determining thymic iNKT selection. Twit Text FOAVip Normal development and function of invariant natural killer T cells in mice with isoglobotrihexosylceramide (iGb3) deficiency ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=17372206 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=17372206 #FOAvip English Wikipedia <ref>{{Cite pmid|17372206}}</ref> Normal development and function of invariant natural killer T cells in mice with isoglobotrihexosylceramide (iGb3) deficiency #MMPMID17372206 Porubsky S; Speak AO; Luckow B; Cerundolo V; Platt FM; Grone HJ Proc Natl Acad Sci U S A 2007[Apr]; 104 (14): 5977-82 PMID17372206show ga CD1d-restricted natural killer T (NKT) cells, expressing the invariant T cell antigen receptor (TCR) chain encoded by Valpha14-Jalpha18 gene segments in mice and Valpha24-Jalpha18 in humans [invariant NKT (iNKT) cells], contribute to immunoregulatory processes, such as tolerance, host defense, and tumor surveillance. iNKT cells are positively selected in the thymus by CD1d molecules expressed by CD4(+)/CD8(+) cortical thymocytes. However, the identity of the endogenous lipid(s) responsible for positive selection of iNKT cells remains unclear. One candidate lipid proposed to play a role in positive selection is isoglobotrihexosylceramide (iGb3). However, no direct evidence for its physiological role has been provided. Therefore, to directly investigate the role of iGb3 in iNKT cell selection, we have generated mice deficient in iGb3 synthase [iGb3S, also known as alpha1-3galactosyltransferase 2 (A3galt2)]. These mice developed, grew, and reproduced normally and exhibited no overt behavioral abnormalities. Consistent with the notion that iGb3 is synthesized only by iGb3S, lack of iGb3 in the dorsal root ganglia of iGb3S-deficient mice (iGb3S(-/-)), as compared with iGb3S(+/-) mice, was confirmed. iGb3S(-/-) mice showed normal numbers of iNKT cells in the thymus, spleen, and liver with selected TCR Vbeta chains identical to controls. Upon administration of alpha-galactosylceramide, activation of iNKT and dendritic cells was similar in iGb3S(-/-) and iGb3S(+/-) mice, as measured by up-regulation of CD69 as well as intracellular IL-4 and IFN-gamma in iNKT cells, up-regulation of CD86 on dendritic cells, and rise in serum concentrations of IL-4, IL-6, IL-10, IL-12p70, IFN-gamma, TNF-alpha, and Ccl2/MCP-1. Our results strongly suggest that iGb3 is unlikely to be an endogenous CD1d lipid ligand determining thymic iNKT selection. |Animals[MESH] |Antigens, CD/metabolism[MESH] |Antigens, Differentiation, T-Lymphocyte/metabolism[MESH] |B7-2 Antigen/metabolism[MESH] |Chemokine CCL2/blood[MESH] |Chromatography, High Pressure Liquid[MESH] |Galactosyltransferases/*genetics/*metabolism[MESH] |Globosides/*deficiency/genetics[MESH] |Heterozygote[MESH] |Humans[MESH] |Interferon-gamma/metabolism[MESH] |Interleukin-10/blood[MESH] |Interleukin-12/blood[MESH] |Interleukin-4/blood/metabolism[MESH] |Interleukin-6/blood[MESH] |Killer Cells, Natural/*immunology/*metabolism[MESH] |Lectins, C-Type[MESH] |Mice[MESH] |Mice, Knockout[MESH] |Models, Biological[MESH] |Tumor Necrosis Factor-alpha/blood[MESH]Normal development and function of invariant natural killer T cells in(epmc).pdf DeepDyve Pubget Overpricing