Activation of T lymphocytes results in an increase inH-2-encoded neuraminidase

Abstract

The endogenous neuraminidase activity of various mouse lymphoid subpopulations and tissue compartments was examined by a sensitive fluorometric assay. These analyses indicated that activated T lymphocytes possessed a significantly higher level of intracellular neuraminidase than activated B or resting T or B lymphocytes. Examination of the level of neuraminidase in bone marrow, thymus, lymph node, and unfractionated spleen indicated that these lymphoid tissues contained significantly less neuraminidase than was detected in stimulated T cells. Kinetic studies revealed that the majority of the increase in neuraminidase activity occurred between 24 and 48 h following stimulation. Analysis of activated T lymphocytes prepared from a panel of inbred mouse strains indicated that cells from mice of the H-2v haplotype, which possess the Neu-1a allele and are deficient in liver neuraminidase, exhibited a level of activity which was significantly lower than that detected in stimulated T cells from other mouse strains. These results indicate that the endogenous neuraminidase activity of T lymphocytes increases upon stimulation, and that the level of this enzyme activity in lymphoid cells is also controlled by the Neu-1 locus, which is located in the H-2 region of the major histocompatibility complex.

Cutting Edge: Oseltamivir Decreases T Cell GM1 Expression and Inhibits Clearance of Respiratory Syncytial Virus: Potential Role of Endogenous Sialidase in Antiviral Immunity

“…However, it is possible that an oseltamivir-sensitive endogenous sialidase acts on a substrate other than GSLs to regulate antiviral immunity. For instance, it is known that activated T cells have increased sialidase activity and also have hyposialyated MHC class I molecules (12,26). In our experimental system, oseltamivir treatment had no effect on ex vivo lung mononuclear cell sialidase activity induced by RSV infection (data not shown).…”

“…There are three known sialidases in mice and humans, neu-1, neu-2, and neu-3 (13). Neu-1 and neu-3 are induced in T cells by TCR stimulation, and these enzymes regulate T cell cytokine expression (11,13,26). These studies led to the hypothesis that GSL metabolism plays a role in T cell regulation and cytokine expression (10).…”

Molecular pathology of NEU1 gene in sialidosis

“…Sialidase is overexpressed during the activation of T cells, B cells, macrophages, and neutrophils [Landolfi et al, 1985;Landolfi and Cook, 1986;Cross and Wright, 1991] (N. Stamatos, private communication). The induced enzyme is targeted to the plasma membrane and is responsible for processing different molecules expressed on the cell surface, resulting in their hyposialylation [Chen et al, 1997].…”

“…In activated B cells, sialidase participates in converting the so-called vitamin D3-binding protein into a macrophage activating factor (MAF) [Yamamoto and Kumashiro, 1993;Naraparaju and Yamamoto, 1994;Yamamoto and Naraparaju, 1996a,b]. Consequently, immune cells with genetic or induced sialidase deficiency fail to synthesize IL4, and become less responsive for antigen-presenting cells or fail to produce MAF and/or synthesize IL4 [Landolfi et al, 1985;Yamamoto and Kumashiro, 1993;Chen et al, 1997]. In mice, sialidase deficiency results in the welldocumented impaired activation of lymphocytes and macrophages [Landolfi et al, 1985;Yamamoto and Kumashiro, 1993;Chen et al, 1997].…”

“…Consequently, immune cells with genetic or induced sialidase deficiency fail to synthesize IL4, and become less responsive for antigen-presenting cells or fail to produce MAF and/or synthesize IL4 [Landolfi et al, 1985;Yamamoto and Kumashiro, 1993;Chen et al, 1997]. In mice, sialidase deficiency results in the welldocumented impaired activation of lymphocytes and macrophages [Landolfi et al, 1985;Yamamoto and Kumashiro, 1993;Chen et al, 1997]. Similarly in humans, sialidase deficiency may account for frequent infections observed in sialidosis patients, which can result from the reduced capacity of immune cells to produce cytokines and antibodies, leading to partial immunodeficiency.…”