Thymoma epithelial cells secrete thymic hormone but do not express class II antigens of the major histocompatibility complex.

Savino, Wilson; Manganella, G.; Verley, J. M.; Wolff, Annie; Berrih, S; Levasseur, P; Binet, J P; Dardenne, Mireille; Bach, Jean‐François

doi:10.1172/jci112069

Cited by 33 publications

(17 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although MHC class I molecules were expressed on the thymoma neoplastic epithelial cells at a level comparable to that on normal thymic epithelial cells, expression of MHC class II molecules was generally decreased and varied from case to case, consistent with previous reports [19][20][21][22]. In addition, interestingly, there was a significant correlation between the expression of MHC class II molecules and the proportion of CD3 þ cells among the CD4 þ CD8 ¹ subset in a thymoma.…”

Section: Discussionsupporting

confidence: 90%

“…The interaction between the T cell antigen receptor (TCR) on thymocytes and MHC antigen on thymic epithelium is believed to play an important role in selection of mature thymocytes [16][17][18]. Previous immunohistochemical analyses have demonstrated a reduced expression of MHC class II molecules on thymoma epithelial cells [19][20][21][22]. Thus, it seems reasonable to speculate that the abnormal T cell development in thymomas might be accompanied by the altered selection of newly generated T cells, and this in turn might lead to autoimmune disease [15].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Inoue

Okumura²,

Miyoshi³

et al. 1999

Clinical and Experimental Immunology

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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

Inoue

Okumura²,

Miyoshi³

et al. 1999

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…Marked increases in thymocyte MHCII expression in GBA KO mice might, thus, impact cell fate. MHCII may enable DP thymocyte depletion through pathological apoptosis, while stimulating positive selection during T-cell maturation (20,21). The latter may underlie the accumulation of mature CD4 + and CD8 + single-positive cells in GBA KO thymocytes in severe disease.…”

Section: Discussionmentioning

confidence: 99%

Gaucher disease geneGBAfunctions in immune regulation

Liu

Halene

Yang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Inherited deficiency of acid β-glucosidase (GCase) due to biallelic mutations in the GBA (glucosidase, β, acid) gene causes the classic manifestations of Gaucher disease (GD) involving the viscera, the skeleton, and the lungs. Clinical observations point to immune defects in GD beyond the accumulation of activated macrophages engorged with lysosomal glucosylceramide. Here, we show a plethora of immune cell aberrations in mice in which the GBA gene is deleted conditionally in hematopoietic stem cells (HSCs). The thymus exhibited the earliest and most striking alterations reminiscent of impaired T-cell maturation, aberrant B-cell recruitment, enhanced antigen presentation, and impaired egress of mature thymocytes. These changes correlated strongly with disease severity. In contrast to the profound defects in the thymus, there were only limited cellular defects in peripheral lymphoid organs, mainly restricted to mice with severe disease. The cellular changes in GCase deficiency were accompanied by elevated T-helper (Th)1 and Th2 cytokines that also tracked with disease severity. Finally, the proliferation of GCase-deficient HSCs was inhibited significantly by both GL1 and Lyso-GL1, suggesting that the “supply” of early thymic progenitors from bone marrow may, in fact, be reduced in GBA deficiency. The results not only point to a fundamental role for GBA in immune regulation but also suggest that GBA mutations in GD may cause widespread immune dysregulation through the accumulation of substrates.

show abstract

“…Okumura and co‐workers69 have suggested that the lack of functional medulla in the tumor might result in defective negative selection of T cells, favoring autosensitization against locally expressed autoantigens, such as AChR. Savino and colleagues72 showed that thymoma epithelial cells are defective in the expression of HLA class II molecules known to play an essential role in intrathymic T‐cell differentiation, which might explain thymoma‐associated defects in the thymic selection of T cells. Those investigators had previously shown that expression of a differentiation factor for human thymic epithelium—recognized by the anti‐p19 monoclonal antibody—is lost in thymomas, suggesting that, during malignant transformation, thymic epithelial cells acquire severe defects likely to give rise to defective T‐cell selection 73…”

Section: Evidence For Thymic Involvement In Mgmentioning

confidence: 99%

The thymus in myasthenia gravis: Site of “innate autoimmunity”?

et al. 2011

View full text Add to dashboard Cite

Myasthenia gravis (MG) is an autoimmune disorder caused, in most cases, by autoantibodies against components of the neuromuscular junction, frequently the acetylcholine receptor (AChR), and less often the muscle-specific kinase receptor. The thymus plays a major role in the pathogenesis of MG with anti-AChR antibodies: it shows marked pathologic alterations (hyperplastic or tumoral) in most AChR-positive patients and contains the elements required to initiate and sustain an autoimmune reaction (AChR autoantigen, AChR-specific T cells, and autoantibody-secreting plasma cells). In this study we review early and more recent findings implicating the thymus as site of AChR autosensitization in MG and briefly discuss the therapeutic role of thymectomy. We also summarize data showing that the MG thymus is in a state of chronic inflammation, and we review emerging evidence of a viral contribution to the onset and maintenance of the thymic autoimmune response.

show abstract

Thymoma epithelial cells secrete thymic hormone but do not express class II antigens of the major histocompatibility complex.

Cited by 33 publications

References 35 publications

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

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

Gaucher disease geneGBAfunctions in immune regulation

The thymus in myasthenia gravis: Site of “innate autoimmunity”?

Contact Info

Product

Resources

About