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

Ichikawa,Ayako; Miyoshi,Hiroaki; Arakawa,Fumiko; Kiyasu,Junichi; Sato,Kensaku; Niino,Daisuke; Kimura,Yoshizo; Yoshida,Maki; Kawano,Riko; Muta,Hiroko; Sugita,Yasuo; Ohshima,Koichi

doi:10.3892/ol.2017.6067

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

Authors:
- Ayako Ichikawa
- Hiroaki Miyoshi
- Fumiko Arakawa
- Junichi Kiyasu
- Kensaku Sato
- Daisuke Niino
- Yoshizo Kimura
- Maki Yoshida
- Riko Kawano
- Hiroko Muta
- Yasuo Sugita
- Koichi Ohshima
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Affiliations: Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830 0011, Japan, Biostatistics Center, School of Medicine, Kurume University, Kurume, Fukuoka 830 0011, Japan
Published online on: April 21, 2017 https://doi.org/10.3892/ol.2017.6067
Pages: 4611-4618
Copyright: © Ichikawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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