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Published online before print October 6, 2006

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1105692

Received for publication November 27, 2005.
Revised August 30, 2006.
Accepted for publication September 11, 2006.

Article

Sialidase expression in activated human T lymphocytes influences production of IFN-

Xinli Nan ^*, Ivan Carubelli ^*, and Nicholas M. Stamatos ^*@

*Institute of Human Virology, University of Maryland, Baltimore, Maryland, USA; and Division of Infectious Diseases, Department of Medicine, University of Maryland Medical Center, Baltimore, Maryland, USA

^@ To whom correspondence should be addressed. E-mail: stamatos{at}umbi.umd.edu.

	Abstract

Sialidases influence cellular activity by removing terminal sialic acid from glycoproteins and glycolipids. Four genetically distinct sialidases (Neu1-4) have been identified in mammalian cells. In this study, we demonstrate that only lysosomal Neu1 and plasma membrane-associated Neu3 are detected in freshly isolated and activated human T lymphocytes. Activation of lymphocytes by exposure to anti-CD3 and anti-CD28 IgG resulted in a ninefold increase in Neu1-specific activity after growth of cells in culture for 5 days. In contrast, the activity of Neu3 changed minimally in activated lymphocytes. The increase in Neu1 enzyme activity correlated with increased synthesis of Neu1-specific mRNA. Neu1 was present on the surface of freshly isolated and activated CD4 and CD8 T lymphocytes, as determined by staining intact cells with anti-Neu1 IgG and analysis by flow cytometry and by Western blot analysis of biotin-labeled cell surface proteins. Cell surface Neu1 was found tightly associated with a subunit of protective protein cathepsin A. Compared with freshly isolated lymphocytes, activated cells expressed more surface-binding sites for galactose-recognizing lectins Erythrina cristagalli (ECA) and Arachis hypogaea. Growth of cells in the presence of sialidase inhibitors 2,3-dehydro-2-deoxy-N-acetylneuraminic acid or 4-guanidino-2-deoxy-2,3-dehydro-N- acetylneuraminic acid resulted in a smaller increase in number of ECA-binding sites and a greater amount of cell surface sialic acid in activated cells. Inhibition of sialidase activity also resulted in reduced expression of IFN- in activated cells. The down-regulation of IFN- occurred at the transcriptional level. Thus, sialidase activity in activated T lymphocytes contributes to the hyposialylation of specific cell surface glycoconjugates and to the production of IFN-.

Key Words: activation • sialic acid • cytokines

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