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-CD3 epsilon under serum-free conditions , splenocytes from most normal (neu-1(b)) mouse strains directly produ ced IL-4 and other T cell cytokines, However, splenic T cells from SM/ J and B10.SM (H-2(v) neu-1(a)) strain mice, deficient in neu-l sialida se activity, failed to produce IL-4 but produced normal levels of IL-2 following activation. Moreover, sialidase-deficient mice produced mar kedly less IgE and IgG1 Abs following immunization with protein Ags th an did mouse strains with normal neu-1 sialidase activity, Enriched T cells from neu-1(a) mice failed to be effectively primed with exogenou s murine IL-4 to become IL-4-producing cells. Treatment of splenocytes or enriched T cells from neu-1(a) mice with bacterial sialidase prior to activation or IL-4 priming promoted their subsequent capacity to p roduce IL-4. In contrast, activation of T cells from neu-1(b) mice in the presence of a sialidase inhibitor almost completely blocked subseq uent IL-4 production, The presence of IL-4 during priming enhanced T c ell expression of neu-1-specific sialidase activity and increased the membrane expression of asialo-G(M1) compared with T cells activated wi thout IL-4, These results suggest that T cell-associated neu-1 sialida se is required for early IL-4 production by splenic T cells and is inv olved in the IL-4 priming process of conventional T cells to become ac tive IL-4 producers.