title: NKT-associated markers and perforin in hyperplastic thymuses from patients with Myasthenia gravis.
abstract: Immunohistochemical expression of natural killer T (NKT) cell-associated markers (Valpha24 and CD56) and perforin in relation to CD44-highly positive (CD44(high)) cells was studied in hyperplastic thymuses from patients with myasthenia gravis (MG) whose symptoms dramatically improved after thymectomy and compared with non-MG control thymuses. In the control thymuses, Valpha24-positive (Valpha24(+)) and CD56-positive (CD56(+)) cells were sparsely distributed in the medullary area only. In contrast, in hyperplastic MG thymus, Valpha24(+) and CD56(+) cells were more frequent in connective tissue, appeared to have penetrated the thymic parenchyma, and most coexpressed CD44(high). Perforin-positive cells were not present in the control thymus, but were in the connective tissue and perilobular cortical areas in the hyperplastic MG thymus. Most of these perforin-positive cells were CD44(high) and were located near blood vessels. They appeared to have migrated directly from the vascular system and penetrated the thymic parenchyma. Some perforin-positive cells coexpressed Valpha24, CD56, or both. These findings suggest that in this particular type of MG thymus, NKT-like cells may have increased via a CD44- and perforin-mediated mechanism, leading to an imbalance in the immune system that favored an antibody-mediated autoimmunity against the acetylcholine receptor.
authors.affiliation: Department of Neurology, Iwate Medical University, Uchimaru 19-1, Morioka 020-8505, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nagane
authors.forename: K
authors.initials: K
authors.lastname: Utsugisawa
authors.forename: D
authors.initials: D
authors.lastname: Obara
authors.forename: H
authors.initials: H
authors.lastname: Tohgi
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D019002:CD56 Antigen / Q000032:analysis; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D009157:Myasthenia Gravis / Q000276:immunology / Q000473:pathology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013950:Thymus Gland / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D013952:Thymus Hyperplasia / Q000276:immunology / Q000473:pathology*
chemical_list: D015415:Biomarkers; D019002:CD56 Antigen; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054353:Perforin