Detection of Tax-specific CTLs in lymph nodes of adult T-cell leukemia/lymphoma patients and its association with Foxp3 positivity of regulatory T-cell function
| Autor: | Hiroko Muta, Maki Yoshida, Hiroaki Miyoshi, Koichi Ohshima, Kensaku Sato, Junichi Kiyasu, Daisuke Niino, Riko Kawano, Yasuo Sugita, Yoshizo Kimura, Ayako Ichikawa, Fumiko Arakawa |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
human T-cell lymphotropic virus Cancer Research adult T-cell leukemia/lymphoma Regulatory T cell chemical and pharmacologic phenomena Major histocompatibility complex Adult T-cell leukemia/lymphoma 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases Medicine Cytotoxic T cell regulatory T-cell biology Tax-specific cytotoxic T-cell business.industry FOXP3 hemic and immune systems Articles medicine.disease Lymphoma CTL 030104 developmental biology medicine.anatomical_structure Oncology Foxp3 030220 oncology & carcinogenesis Cancer research biology.protein business CD8 |
| Zdroj: | Oncology Letters |
| ISSN: | 1792-1082 1792-1074 |
| DOI: | 10.3892/ol.2017.6067 |
| Popis: | Human T-cell lymphotropic virus type (HTLV)-1 Tax is a viral protein that has been reported to be important in the proliferation of adult T-cell leukemia/lymphoma (ATLL) cells and to be a target of HTLV-1-specific cytotoxic T lymphocytes (CTLs). However, it is not clear how Tax-specific CTLs behave in lymph nodes of ATLL patients. The present study analyzed the immunostaining of Tax-specific CTLs. Furthermore, ATLL tumor cells are known to be positive for forkhead box P3 (Foxp3)and to have a regulatory T (Treg)-cell-like function. The association between T-reg function and number and activity of Tax-specific CTLs was also investigated. A total of 15 ATLL lymphoma cases with human leukocyte antigen (HLA)-A24, for which Tax has a high affinity, were selected from the files of the Department of Pathology, School of Medicine, Kurume University (Kurume, Japan) using a polymerase chain reaction (PCR) method. Immunostaining was performed for cluster of differentiation (CD) 20, CD3, CD4, CD8, T-cell intracellular antigen-1 and Foxp3 in paraffin sections, and for Tax, interferon γ and HLA-A24 in frozen sections. In addition, the staining of Tax-specific CTLs (HLA-A24-restricted) was analyzed by MHC Dextramer® assay in frozen sections. In addition, the messenger RNA expression of Tax and HTLV-1 basic leucine zipper factor were also evaluated by reverse transcription-PCR. Immunohistochemical staining of Tax protein in lymphoma tissue revealed the presence of positive lymphoma cells ranging from 5 to 80%, and immunohistochemical staining of HLA-A24 revealed the presence of positive lymphoma cells ranging from 1 to 95%. The expression of Tax and HLA-A24 was downregulated by viral function. Foxp3, a marker for Treg cells, was expressed in 0–90% of cells. Several cases exhibited Tax-specific CTL (HLA-A24-restricted)-positive cells, and there was an inverse correlation between Tax-specific CTLs and Foxp3. However, neither Tax nor HLA-A24 expression was associated with CTL or Foxp3. Our study indicated the possibility that ATLL cells, which expressed Tax, target of CTL, evade the CTL-mediated immune control by expression of Foxp3 as a Treg function. |
| Databáze: | OpenAIRE |
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