title: Selective impairment of CD43-mediated T cell activation in the Wiskott-Aldrich syndrome.
abstract: The Wiskott-Aldrich syndrome (WAS) is associated with defective glycosylation and altered membrane expression of the leukocyte sialoglycoprotein CD43. To investigate whether such modifications of CD43 are relevant to T cell dysfunction in WAS, we have analyzed peripheral blood mononuclear cells from WAS patients for proliferative responses to both CD43-interacting and other T cell mitogenic stimuli. While patient lymphocytes proliferated in response to phytohaemagglutinin, concanavalin A, interleukin-2 and neuraminidase/galactose oxidase, no responses were elicited upon attempted triggering of the CD43 signalling pathway using periodate or anti-CD43 antibody. Cells from four of five patients with clinical profiles resembling, but not identical, to that of classic WAS also failed to respond to periodate or anti-CD43 antibody stimulation. These results indicate that the aberrant expression of CD43 on WAS lymphocytes is associated with selective impairment of CD43-induced T cell proliferation and that detection of this defect may be useful in the diagnosis of WAS and its variant forms.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: K A
authors.initials: KA
authors.lastname: Siminovitch
authors.forename: W L
authors.initials: WL
authors.lastname: Greer
authors.forename: B
authors.initials: B
authors.lastname: Axelsson
authors.forename: L A
authors.initials: LA
authors.lastname: Rubin
authors.forename: A
authors.initials: A
authors.lastname: Novogrodsky
authors.forename: M
authors.initials: M
authors.lastname: Peacocke
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies; D015703:Antigens, CD / Q000737:chemistry; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D006031:Glycosylation; D006801:Humans; D066298:In Vitro Techniques; D051917:Leukosialin; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D015394:Molecular Structure; D012795:Sialoglycoproteins / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014923:Wiskott-Aldrich Syndrome / Q000175:diagnosis / Q000276:immunology*
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D015415:Biomarkers; D051917:Leukosialin; D008934:Mitogens; C465014:SPN protein, human; D012795:Sialoglycoproteins