NXT-associated markers and perforin in hyperplastic thymuses from patients with myasthenia gravis

Immunohistochemical expression of natural killer T (NKT) cell-associated markers (V alpha 24 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, V alpha 24-positive (V alpha 24(+)) and CD56-positive (CD56(+)) cells were sparsely distributed in the medullary area only. In contrast, in hyperplastic MG thymus, V alpha 24(+) 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 V alpha 24, 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. (C) 2001 John Wiley & Sons, Inc.