title: Small changes in lymphocyte development and activation in mice through tissue-specific alteration of heparan sulphate.
abstract: We have examined the role of heparan sulphate in lymphocyte development and activation in mice by conditionally deleting the genes encoding the heparan sulphate biosynthetic enzymes N-deacetylase/N-sulphotransferase-1 and -2 (Ndst1 and Ndst2) and glucuronic acid/N-acetylglucosamine co-polymerase-1 (Ext1) in T cells and B cells, respectively. Ndst1 and Ndst2 are the only Ndst isoforms in T cells. In T-cell Ndst-deficient mice there were normal ratios of CD4(+)/CD8(+) cells in the blood, spleen and thymus, indicating no dramatic effect on development. However, Ndst-deficient T cells were hyperresponsive to low-level activation, suggesting that cell surface heparan sulphate plays a role in T-cell proliferation. The hyperresponsive state correlated with a decrease in cell surface heparan sulphate that occurs in response to activation in wild-type cells. There was a slight change in the number of developing B cells in B-cell Ext1-deficient mice, but the alteration did not cause a change in antibody production. These findings demonstrate that cell surface heparan sulphate may not play a crucial role in lymphocyte development, but can modulate the sensitivity of T cells to activation.
authors.affiliation: Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Omai B
authors.initials: OB
authors.lastname: Garner
authors.forename: Yu
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Esko
authors.forename: Vibeke
authors.initials: V
authors.lastname: Videm
mesh_terms: D000818:Animals; D016516:CD4-CD8 Ratio; D049109:Cell Proliferation; D002478:Cells, Cultured; D005838:Genotype; D006497:Heparan Sulfate / Q000096:biosynthesis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017351:N-Acetylglucosaminyltransferases / Q000172:deficiency / Q000235:genetics; D013154:Spleen / Q000276:immunology; D015238:Sulfotransferases / Q000172:deficiency / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D000099058:Exostosin 1
chemical_list: D006497:Heparan Sulfate; D017351:N-Acetylglucosaminyltransferases; D015238:Sulfotransferases; D000099058:Exostosin 1; C021350:heparitin sulfotransferase