Two-color flow cytometric analysis of thymic lymphocytes from patients with myasthenia gravis and/or thymoma

Abstract

Phenotypic characteristics of lymphocyte components of the thymus were determined by two-color flow cytometry using monoclonal antibodies to T cell-differentiation antigens and activation antigens, and B cells in eight myasthenia gravis (MG) thymuses and eight thymomas including four associated with MG to clarify the roles of thymus in the diseases. Fifteen normal thymuses and four thymuses from non-MG patients were used as controls. Phenotypes of lymphoid components in thymoma resembled those in normal thymuses, in which the majority of lymphoid cells were immature (common) thymocytes (CD4 +CD8 + or CD1 +CD3 −). The proportions of immature thymocytes, however, were relatively higher and those of mature thymocytes (CD4 +CD8 −, CD4 −CD8 +, CD1 −CD3 + or CD2 +CD3 +) were lower in thymomas than normal thymuses. The results speculate that functions which support further differentiations of immature thymocytes into mature thymocytes are deficient in neoplastic epithelial cells of thymoma. In thymomas, therefore, occasional T cells might escape from the thymic surveillance system which eliminates auto-reactive T cells. Between thymomas associated with MG and those without, however, no significant difference was found in the proportions of thymocytes at various stages of maturation. In nonthymomatous thymuses from MG patients, an increase of both B cells (CD2 −DR + or CD2 −CD21 +) and activated T cells (CD2 +DR + or CD2 +IL-2R +) was observed. Furthermore, immature thymocytes were significantly decreased and mature thymocytes were increased in the MG thymuses, as compared with normal thymuses, non-MG thymuses, and thymomas. These alterations were relevant to the histological findings observed in MG thymuses such as thymic involutions and germinal center formations: decreased immature thymocytes are considered to reflect thymic involutions, while germinal centers, in which lymphocytes from peripheral lymphoid organs are activated, are responsible for the increase of B cells, activated T cells, and mature T cells. In conclusions, our results suggest that neoplastic epithelial cells of thymomas are functionally deficient and that MG thymuses are immunologically active and resemble peripheral lymphoid organs.