The control of IL-4 gene expression in activated murine T lymphocytes: a novel role for neu-1 sialidase.
IL-4 is important in controlling the development of immune responses. Following activation with anti-CD3epsilon under serum-free conditions, splenocytes from most normal (neu-1b) mouse strains directly produced IL-4 and other T cell cytokines. However, splenic T cells from SM/J and B10.SM (H-2v, neu-1a) strain 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 Abs following immunization with protein Ags than did mouse strains with normal neu-1 sialidase activity. Enriched T cells from neu-1a mice failed to be effectively primed with exogenous murine IL-4 to become IL-4-producing cells. 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 subsequent 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-G(M1) compared with T cells activated without IL-4. These results suggest that T cell-associated neu-1 sialidase is required for early IL-4 production by splenic T cells and is involved in the IL-4 priming process of conventional T cells to become active IL-4 producers.
Chen
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XP
Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Enioutina
E Y
EY
Daynes
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RA
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005677:G(M1) Ganglioside / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism
D015847:Interleukin-4; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; C110128:Neu1 protein, mouse; D009439:Neuraminidase