title: TcR-alpha/beta(+) CD4(-)CD8(-) T cells in humans with the autoimmune lymphoproliferative syndrome express a novel CD45 isoform that is analogous to murine B220 and represents a marker of altered O-glycan biosynthesis.
abstract: Autoimmune lymphoproliferative syndrome (ALPS), caused by inherited defects in apoptosis secondary to mutations in genes encoding Fas/CD95/APO-1 and Fas ligand (Fasl)/CD95L, is characterized by nonmalignant lymphadenopathy and splenomegaly, increased T cell receptor alpha/beta(+) CD4(-)CD8(-) T cells (alpha/beta(+) double-negative T cells [alpha/beta(+)-DNT cells]), autoimmunity, hypergammaglobulinemia, and cytokine abnormalities. The alpha/beta(+)-DNT cells are immunophenotypically and functionally similar to alpha/beta(+)-DNT cells that accumulate in lpr and gld mice, which bear genetic mutations in Fas and FasL. In these mice, alpha/beta(+)-DNT cells express the B-cell-specific CD45R isoform B220. We show that alpha/beta(+)-DNT cells of ALPS patients, with either Fas or FasL mutations, also express B220. In addition, also similar to LPR/gLD mice, they have an unusual population of B220-positive CD4(+) T cells. B220 expression, together with our finding of characteristic lectin binding profiles, demonstrates that cell surface O-linked glycoproteins have undergone specific modifications, which may have consequences for lymphocyte trafficking, cell-cell interactions, and access to alternative apoptosis pathways.
authors.affiliation: Immunology Service, Warren G. Magnuson Clinical Center, Bethesda, Maryland 20892, USA. BleesingJacobH@uams.edu
authors.forename: J J
authors.initials: JJ
authors.lastname: Bleesing
authors.forename: M R
authors.initials: MR
authors.lastname: Brown
authors.forename: J K
authors.initials: JK
authors.lastname: Dale
authors.forename: S E
authors.initials: SE
authors.lastname: Straus
authors.forename: M J
authors.initials: MJ
authors.lastname: Lenardo
authors.forename: J M
authors.initials: JM
authors.lastname: Puck
authors.forename: T P
authors.initials: TP
authors.lastname: Atkinson
authors.forename: T A
authors.initials: TA
authors.lastname: Fleisher
mesh_terms: D001327:Autoimmune Diseases / Q000276:immunology*; D015415:Biomarkers; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis*; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000032:analysis; D011134:Polysaccharides / Q000096:biosynthesis*; D020033:Protein Isoforms; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013601:T-Lymphocytes / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D015704:CD4 Antigens; D016827:CD8 Antigens; D008562:Membrane Glycoproteins; D011134:Polysaccharides; D020033:Protein Isoforms; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017493:Leukocyte Common Antigens