Impaired expression of MHC class II molecules in response to interferon-gamma (IFN-gamma) on human thymoma neoplastic epithelial cells

Abstract

A human thymoma is a neoplasm derived from the thymic epithelial cell, and is well known for its association with autoimmune diseases, especially myasthenia gravis. The neoplastic epithelial cells of thymoma clearly retain thymic epithelial functions, but the development of T cells in thymoma is somewhat impaired. In this study, we quantified by flow cytometry the in vitro expression of MHC molecules on neoplastic epithelial cells precultured with IFN-gamma. While MHC class I expression was comparable with that on normal thymic epithelial cells, the level of MHC class II molecules on neoplastic epithelial cells was lower than in controls, and also varied greatly from case to case. Additionally, there was a significant positive correlation between the expression level of MHC class II and the proportion of mature CD3+ cells in the CD4+CD8- subset. Thus, accumulation of CD3-CD4+CD8- cells in thymoma may result from impaired expression of the MHC class II molecules, suggesting that the function of the neoplastic epithelial cells might determine the maturation and the positively selected repertoire of T cells in thymomas.

Fig. 1

A representative result of the CD3 expression in each subset defined by CD4 and CD8 expressions (case 6).

Fig. 2

(a) HLA-ABC (MHC class I) expression on epithelial cells (upper) and CD3 expression among CD4⁻CD8⁺ lymphocytes (lower) in typical cases. Solid lines show the negative control stains. The expression level was judged by D value in Kolmogorov–Smirnov statistics for MHC and the percentage for CD3. A normal thymus is presented as a positive control. (b) HLA-ABC expression of all thymoma cases and normal thymi. Thymoma: D = 0.93 ± 0.05 versus normal thymus: D = 0.92 ± 0.05, not significant (NS).

Fig. 3

(a) HLA-DP/DQ/DR (MHC class II) expression on epithelial cells (upper) and CD3 expression among CD4⁺CD8⁻ lymphocytes (lower) in typical cases. Solid lines show the negative control stains. The expression level was judged by D value in Kolmogorov–Smirnov statistics for MHC and the percentage for CD3. A normal thymus is presented as a positive control. (b) HLA-DP/DQ/DR expression of all thymoma cases and normal thymi. Thymoma: D = 0.44 ± 0.17 versus normal thymus: D = 0.82 ± 0.08; P < 0.01, significant by unpaired t-test.

Fig. 4

The relationship between HLA-DP/DQ/DR expression and the proportion of CD3⁺ cells among the CD4⁺CD8⁻ subset. ○, Patients with positive autoantibodies.