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Small changes in lymphocyte development and activation in mice through tissue‐specific alteration of heparan sulphate
Author(s) -
Garner Omai B.,
Yamaguchi Yu,
Esko Jeffrey D.,
Videm Vibeke
Publication year - 2008
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.02856.x
Subject(s) - biology , heparan sulfate , cell , t cell , microbiology and biotechnology , cell growth , lymphocyte , spleen , cd8 , biochemistry , immunology , immune system
Summary 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.