Altered T cell development in human thymoma is related to impairment of MHC class II transactivator expression induced by interferon-gamma (IFN-<i>γ</i>)

Kadota, Yoshihisa; Okumura, Meinoshin; Miyoshi, Shinichiro; Kitagawa-Sakakida, Satoru; Inoue, Masahiro; Shiono, Hiroshi; Maeda, Yuka; Kinoshita, Taroh; Shirakura, R; Matsuda, Hikaru

doi:10.1046/j.1365-2249.2000.01256.x

Cited by 43 publications

(26 citation statements)

References 52 publications

(72 reference statements)

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“…26 Recent research on the regulation of HLA-DR expression has shown that class II transactivator (CIITA) is a master regulator of HLA-DR molecules, 27 and CIITA expression was downregulated in neoplastic epithelial cells of thymomas as compared with normal thymi. 28 Further, in thymomas, the proportion of CD3 + cells in the CD4 + CD8 − T-cell subset was signifi cantly correlated with HLA-DR (Fig. 3) and CIITA expression.…”

Section: Difference In T-cell Development Between the Normal Thymus Amentioning

confidence: 79%

Immunological function of thymoma and pathogenesis of paraneoplastic myasthenia gravis

Okumura

Fujii

Shiono

et al. 2008

Gen Thorac Cardiovasc Surg

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Thymoma and thymic carcinoma are the representative tumors arising from the thymic epithelium. Thymoma is well known for association with autoimmune diseases including myasthenia gravis, suggesting its biological activity. Herein, recent progress in research of thymoma is reviewed with reference to its immunological function. Myasthenia gravis is frequently associated with WHO type B1 and B2 thymomas. These types of thymomas hold a significant number of CD4(+)CD8(+) double-positive T cells, and at the same time, the neoplastic epithelial cells express HLA-DR molecules at a slightly reduced level compared with the normal thymus. The impaired expression of HLA-DR molecules in neoplastic epithelial cells of thymomas possibly affects positive selection of CD4(+)CD8(-) single-positive T cells and may result in alteration of its repertoire. The function of thymoma neoplastic cells as the cortical epithelium of the thymus and the morphological resemblance of thymomas to the cortex suggest that thymoma is of cortical epithelial origin; this might imply that thymoma lacks the functional medulla where professional antigen-presenting cells are engaged in negative selection. These findings suggest that thymoma generates autoreactive T cells causing autoimmunity. Further investigation on immunological function of thymoma is supposed to elucidate the pathogenesis of thymoma-related autoimmunity and the high affinity of thymoma with myasthenia gravis. In addition, studying the biology of thymoma is also expected to contribute to further understanding of T-cell development and immunological tolerance in the human, because thymoma can be considered an acquired thymus.

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Section: Difference In T-cell Development Between the Normal Thymus Amentioning

confidence: 79%

Immunological function of thymoma and pathogenesis of paraneoplastic myasthenia gravis

Okumura

Fujii

Shiono

et al. 2008

Gen Thorac Cardiovasc Surg

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“…These observations suggested that thymoma was responsible for the export of auto-reactive CD4 + T cells whose generation could result from defects in intra-thymic selection [12,14]. More recently, a defect of T cell regulatory function has also been described.…”

Section: Discussionmentioning

confidence: 98%

Paraneoplastic diseases associated with thymoma

et al. 2007

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“…MG-associated TM are rich in autoreactive T cells, compared with hyperplasia MG. These autoreactive T cells are positively selected and exported to the periphery where they are activated to provide help for autoantibody-producing B cells [6,7].…”

Section: Myasthenia Gravis (Mg) Is a Prototypical Cd4mentioning

confidence: 99%

T Helper Type 17 Cells Expand in Patients with Myasthenia‐Associated Thymoma

Wang¹,

Wang²,

Chen³

et al. 2012

Scand J Immunol

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Myasthenia gravis (MG) is a prototypical CD4+ T cell–dependent autoimmune disease mediated by anti‐acetylcholine receptor autoantibodies (AChR‐Abs). Certain subsets of helper T cells are suggested to be involved in the pathogenesis of MG, including Th1 and regulatory T cells (Treg). However, whether the recently identified Th17 cells play a role in the development of MG and its prognosis is still unknown. Here, we demonstrated that Th17 cells and their associated cytokines are increased, while the Treg cells are decreased in the peripheral blood mononuclear cells (PBMCs) from MG patients with thymomas (TM), but not from those with normal thymus (NT) or thymic hyperplasia (TH). Furthermore, the quantity of Th17 cells correlates with the quantitative myasthenia gravis (QMG) score in patients with TM. We also found a significant positive relationship between the frequency of Th17 cells (%) and the concentration of AChR antibodies in patients with MG. Therefore, the Th17/Treg imbalance in TM may suggest MG with certain pathological subtype, and the increase in Th17 cells may reveal the severity of the disease, which is valuable in the diagnosis and choice of therapeutic strategy for patients with MG.

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Altered T cell development in human thymoma is related to impairment of MHC class II transactivator expression induced by interferon-gamma (IFN-γ)

Cited by 43 publications

References 52 publications

Immunological function of thymoma and pathogenesis of paraneoplastic myasthenia gravis

Immunological function of thymoma and pathogenesis of paraneoplastic myasthenia gravis

Paraneoplastic diseases associated with thymoma

T Helper Type 17 Cells Expand in Patients with Myasthenia‐Associated Thymoma

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