Research article

Induction of lysosomal and plasma membrane-bound sialidases in human T-cells via T-cell receptor

Peng WANG, Ji ZHANG, Hong BIAN, Ping WU, Reshma KUVELKAR, Ted T. KUNG, Yvette CRAWLEY, Robert W. EGAN, M. Motasim BILLAH


Among the three isoenzymes of neuraminidase (Neu) or sialidase, Neu-1 has been suggested to be induced by cell activation and to be involved in IL (interleukin)-4 biosynthesis in murine T-cells. In the present study, we found that antigen-induced airway eosinophilia, a typical response dependent on Th2 (T-helper cell type 2) cytokines, as well as mRNA expression of Th2 cytokines, including IL-4, are suppressed in Neu-1-deficient mice, thereby demonstrating the in vivo role of murine Neu-1 in regulation of Th2 cytokines. To elucidate the roles of various sialidases in human T-cell activation, we investigated their tissue distribution, gene induction and function. Neu-1 is the predominant isoenzyme at the mRNA level in most tissues and cells in both mice and humans, including T-cells. T-cells also have significant levels of Neu-3 mRNAs, albeit much lower than those of Neu-1, whereas the levels of Neu-2 mRNAs are minimal. In human T-cells, both Neu-1 and Neu-3 mRNAs are significantly induced by T-cell-receptor stimulation, as is sialidase activity against 4-methylumbelliferyl-N-acetylneuramic acid (a substrate for both Neu-1 and Neu-3) and the ganglioside GD1a [NeuAcα2-3Galβ1-3GalNAcβ1-4(NeuAcα2-3)Galβ1-4Glcβ1-cer] (a substrate for Neu-3, but not for Neu-1). The expression of the two sialidase genes may be under differential regulation. Western blot analysis and enzymic comparison with recombinant sialidases have revealed that Neu-3 is induced as a major isoform in activated cells. The induction of Neu-1 and Neu-3 in T-cells is unique. In human monocytes and neutrophils stimulated with various agents, the only observation of sialidase induction has been by IL-1 in neutrophils. Functionally, a major difference has been observed in Jurkat T-cell lines over-expressing Neu-1- and Neu-3. Upon T-cell receptor stimulation, IL-2, interferon-γ, IL-4 and IL-13 are induced in the Neu-1 line, whereas in the Neu-3 line the same cytokines are induced, with the exception of IL-4. Taken together, these results suggest an important immunoregulatory role for both Neu-1 and Neu-3 in humans.

  • cytokine
  • gene regulation
  • T-lymphocyte
  • neuraminidase
  • sialidase


  • Abbreviations used: BAL, bronchoalveolar lavage; GD1a, NeuAcα2-3Galβ1-3GalNAcβ1-4(NeuAcα2-3)Galβ1-4Glcβ1-cer; GD1b, Galβ1-3GalNAcβ1-4(NeuAcα2-8NeuAcα2-3)Galβ1-4Glcβ1-cer; GM3, NeuAcα2-3Galβ1-4Glcβ1-cer; G3PDH, glyceraldehyde-3-phosphate dehydrogenase; GT1b, NeuAcα2-3Galβ1-3GalNAcβ1-4(NeuAcα2-8NeuAcα2-3)Galβ1-4Glcβ1-cer; IFN, interferon; IL, interleukin; LPS, lipopolysaccharide; 4-MU-NANA, 4-methylumbelliferyl-N-acetylneuramic acid; Neu, neuraminidase; Th, T-helper cell; TNF, tumour necrosis factor.