title: T cell response in acute motor axonal neuropathy.
abstract: There is evidence that in the acute axonal motor neuropathy (AMAN) subtype of Guillain-Barré syndrome antibodies to gangliosides, produced through molecular mimicry by antecedent Campylobacter jejuni (C. jejuni) infection, attack gangliosides expressed in human peripheral nerve axolemma, inducing a primary axonal damage. The aim of this study is to investigate whether the T cell response has a role in AMAN pathogenesis. We isolated monocytes from 4 healthy subjects and 5 AMAN patients with antecedent C. jejuni infection and antibodies to GM1 and/or GD1a gangliosides. Immature dendritic cells expressing CD1 molecules cultured with autologous T cells were stimulated with 2 lipopolysaccharides (LPSs) extracted from C. jejuni strains containing GM1 and GD1a-like structures and with GM1 and GD1a. The T cell response to LPSs and to gangliosides was determined by measuring the release of IFN-gamma and TNF-alpha. We observed a T cell response to both LPSs in controls and AMAN patients, whereas only AMAN patients showed T cell reactivity to gangliosides GM1 and GD1a with a tight correlation between T cell reactivity to the ganglioside and individual antibody responses to the same ganglioside. T cells responding to gangliosides were CD1c-restricted CD8 positive and CD27 negative. These findings indicate a contribution of cellular immunity in the pathogenesis of AMAN. A possible role for ganglioside-reactive T cells might be to facilitate the production of antibodies against gangliosides.
authors.affiliation: Neuroimmunology Unit, European Centre for Brain Research, Santa Lucia Foundation, Rome, Italy.
authors.forename: M T
authors.initials: MT
authors.lastname: Cencioni
authors.forename: F
authors.initials: F
authors.lastname: Notturno
authors.forename: C M
authors.initials: CM
authors.lastname: Caporale
authors.forename: B
authors.initials: B
authors.lastname: Creati
authors.forename: V
authors.initials: V
authors.lastname: Prencipe
authors.forename: L
authors.initials: L
authors.lastname: Battistini
authors.forename: A
authors.initials: A
authors.lastname: Uncini
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D018949:Antigens, CD1 / Q000032:analysis; D001369:Axons / Q000276:immunology* / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D002169:Campylobacter Infections / Q000276:immunology* / Q000382:microbiology; D016123:Campylobacter jejuni / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology; D005732:Gangliosides / Q000276:immunology; D006023:Glycoproteins / Q000032:analysis; D020275:Guillain-Barre Syndrome / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000276:immunology* / Q000382:microbiology; D009046:Motor Neurons / Q000276:immunology* / Q000382:microbiology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000172:deficiency; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D000906:Antibodies; D018949:Antigens, CD1; C437944:CD1C protein, human; D005732:Gangliosides; D006023:Glycoproteins; D008070:Lipopolysaccharides; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; C021298:ganglioside, GD1a; D005677:G(M1) Ganglioside; D007371:Interferon-gamma