The control of IL-4 gene expression in activated murine T lymphocytes: a novel role for neu-1 sialidase
Chen, X.P.; Enioutina, E.Y.; Daynes, R.A.
Journal of Immunology 158(7): 3070-3080
1997
ISSN/ISBN: 0022-1767 PMID: 9120259 Document Number: 482045
Following activation with anti-CD3 epsilon under serum-free conditions, splenocytes from normal (neu-1b) mouse strains (C3H/HeN, C57BL/6 and BALB/c) produced interleukin-4 (IL-4) and other T cell cytokines. However, splenic T cells from SM/J and B10.SM (H-2v, neu-1a) mice, deficient in neu-1 sialidase activity, failed to produce IL-4 but produced normal levels of IL-2 following activation. Moreover, sialidase-deficient mice produced markedly less IgE and IgG1 antibodies following immunization with protein antigens than mice strains with normal neu-1 sialidase activity. Treatment of enriched T cells from neu-1a mice with IL-4 failed to initiate IL-4 production. Treatment of splenocytes or enriched T cells from neu-1a mice with bacterial sialidase prior to activation or IL-4 priming promoted their subsequent capacity to produce IL-4. In contrast, activation of T cells from neu-1b mice in the presence of a sialidase inhibitor almost completely blocked IL-4 production. The presence of IL-4 during priming enhanced T cell expression of neu-1-specific sialidase activity and increased the membrane expression of asialo-GM1 compared with T cells activated without IL-4. The results suggested that T cell-associated neu-1 sialidase is required for early IL-4 production by splenic T cells and is involved in the priming of conventional T cells to become active IL-4 producers.