Marked increase in CD44-highly positive cells in hyperplastic thymuses from patients with Myasthenia gravis

To investigate the role of the thymus in the pathogenesis of myasthenia gravis (MG), immunohistochemical expression of CD44, CD45R0, B7-1, and IL-2 was studied in: (1) hyperplastic thymuses of patients with MG whose symptoms markedly improved after thymectomy, (2) remnant thymuses of patients with MG whose symptoms did not respond to thymectomy, and (3) non-MG control thymus. Lymphocytes strongly expressing CD44, a marker for homing lymphocytes and activated memory lymphocytes in adults, were much more frequently observed in hyperplastic MG thymuses than in remnant thymuses and non-MG control thymuses. These CD44-highly positive cells in hyperplastic MG thymuses were for the most part located in the subcapsular and cortical areas but also occasionally in medullary areas. Some of these CD44-highly positive cells coexpress CD45R0. CD44-highly positive cells were located in the vicinity of blood vessels and thus appeared to have migrated directly from extralobular blood vessels. B7-1-positive cells and interleukin (IL)-2-positive cells were also more abundant in the MG patients than in controls and were localized in the proximity of CD44-highly positive cells. These findings suggest that mature T and B cells recirculate into hyperplastic MG thymus via CD44-associated mechanisms and are activated there.