title: Evidence against chronic antigen-specific T lymphocyte activation in myasthenia gravis.
abstract: Myasthenia gravis (MG) is an antigen-specific autoimmune disease caused by antibodies against acetylcholine receptors (AChR) at the post-synaptic membrane of the neuromuscular junction. Clinical and immunological data imply the involvement of AChR-specific T lymphocytes as helper cells for autoantibody production. Direct data to support this hypothesis, however, remain sparse. In the present study, a large population of MG patients was studied for evidence of peripheral blood T cell activation by several assays. Assays based on non-specific measurements of T cell activation as well as assays of antigen-specific clonal expansion were utilized. Levels of soluble IL-2 receptor in serum were modestly elevated in some patients, suggesting T cell activation. However, peripheral blood cells did not show evidence of IL-2 receptor expression or enhanced reactivity to IL-2 in culture. Clonable T cells selected for hypoxanthine phosphoribosyl transferase (hprt) mutation, another non-antigen-specific marker for T cell activation, were not seen with increased frequency except in patients treated with purine analogs. Antigen-specific T cell activation was measured by proliferation assays using heterologous and autologous sources of AChR. Antigen-restimulated peripheral blood cell cultures were cloned by limiting dilution. The vast majority of patients failed to show convincing evidence of AChR specific T cell activation or clonal expansion; only 2 of 44 patients demonstrated clonable autologous AChR-specific T cells. An alternative hypothesis of T cell involvement in MG is proposed in which T cell activation is discontinuous and predominantly directed at antigens other than AChR.
authors.affiliation: Department of Pediatrics, University of Texas Health Science Center, San Antonio 78284-7810, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Infante
authors.forename: P D
authors.initials: PD
authors.lastname: Infante
authors.forename: C E
authors.initials: CE
authors.lastname: Jackson
authors.forename: R J
authors.initials: RJ
authors.lastname: Barohn
authors.forename: J
authors.initials: J
authors.lastname: Tami
authors.forename: E
authors.initials: E
authors.lastname: Iturriaga
authors.forename: S
authors.initials: S
authors.lastname: Talib
authors.forename: E
authors.initials: E
authors.lastname: Kraig
authors.forename: K Z
authors.initials: KZ
authors.lastname: Clarkin
authors.forename: K A
authors.initials: KA
authors.lastname: Krolick
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000918:Antibody Specificity; D002908:Chronic Disease; D002999:Clone Cells / Q000737:chemistry / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D008875:Middle Aged; D009154:Mutation / Q000276:immunology; D009157:Myasthenia Gravis / Q000276:immunology*; D017434:Protein Structure, Tertiary; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology; D012995:Solubility; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D014101:Torpedo
chemical_list: D008565:Membrane Proteins; D011950:Receptors, Cholinergic; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins