Activation of human naïve Th cells increases surface expression of GD3 and induces neoexpression of GD2 that colocalize with TCR clusters.
CD4+ T helper lymphocytes (Th) orchestrate the immune response after their activation by antigen-presenting cells. Activation of naïve Th cells is reported to generate the reduction in surface epitopes of sialic acid (Sia) in α2,3 and α2,6 linkages. In this work, we report that in spite of this glycophenotype, anti-CD3/anti-CD28-activated purified human naïve Th cells show a significant increase in surface Sia, as assessed by metabolic labeling, compared with resting naïve Th cells, suggesting an increased flux of Sia toward Siaα2,8 glycoconjugates. To understand this increase as a result of ganglioside up-regulation, we observed that very early after activation, human naïve Th cells show an increased expression in surface GD3 and neoexpression of surface GD2 gangliosides, the latter clustering with the T cell receptor (TCR). Also, we report that in contrast to GM2/GD2 synthase null mice, lentiviral vector-mediated silencing of the GM2/GD2 synthase in activated human naïve Th cells reduced efficient TCR clustering and downstream signaling, as assessed by proliferation assays and IL-2 and IL-2R expression, pointing to an important role of this enzyme in activation of human naive Th cells.
Laboratorio de Glicobiología Humana, Centro de Investigación en Dinámica Celular, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, México Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca 62210, México.
Tania M
TM
Villanueva-Cabello
INSERM U1197, Paris Sud Université XI, Paul Brousse Hôpital, Villejuif 94807, France.
Rosella
R
Mollicone
Laboratorio de Inmunología Molecular.
Mario E
ME
Cruz-Muñoz
Laboratorio de Inmunología Viral, Facultad de Medicina, Universidad Autónoma del Estado de Morelos, Cuernavaca 62350, México.
Delia V
DV
López-Guerrero
Laboratorio de Glicobiología Humana, Centro de Investigación en Dinámica Celular, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, México duncker@uaem.mx.
Iván
I
Martínez-Duncker
D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D005732:Gangliosides; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; C026226:ganglioside, GD3; C019403:ganglioside, GD2; D017350:N-Acetylgalactosaminyltransferases; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase
GD2; GD3; TCR; Th; sialic