Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ichikawa, Ayako, Miyoshi, Hiroaki, Arakawa, Fumiko, Kiyasu, Junichi, Sato, Kensaku, Niino, Daisuke, Kimura, Yoshizo, Yoshida, Maki, Kawano, Riko, Muta, Hiroko, Sugita, Yasuo, Ohshima, Koichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453040/
https://www.ncbi.nlm.nih.gov/pubmed/28599462
http://dx.doi.org/10.3892/ol.2017.6067
_version_ 1783240562749472768
author Ichikawa, Ayako
Miyoshi, Hiroaki
Arakawa, Fumiko
Kiyasu, Junichi
Sato, Kensaku
Niino, Daisuke
Kimura, Yoshizo
Yoshida, Maki
Kawano, Riko
Muta, Hiroko
Sugita, Yasuo
Ohshima, Koichi
author_facet Ichikawa, Ayako
Miyoshi, Hiroaki
Arakawa, Fumiko
Kiyasu, Junichi
Sato, Kensaku
Niino, Daisuke
Kimura, Yoshizo
Yoshida, Maki
Kawano, Riko
Muta, Hiroko
Sugita, Yasuo
Ohshima, Koichi
author_sort Ichikawa, Ayako
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5453040
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-54530402017-06-08 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 Oncol Lett Articles 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. D.A. Spandidos 2017-06 2017-04-21 /pmc/articles/PMC5453040/ /pubmed/28599462 http://dx.doi.org/10.3892/ol.2017.6067 Text en Copyright: © Ichikawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Ichikawa, Ayako
Miyoshi, Hiroaki
Arakawa, Fumiko
Kiyasu, Junichi
Sato, Kensaku
Niino, Daisuke
Kimura, Yoshizo
Yoshida, Maki
Kawano, Riko
Muta, Hiroko
Sugita, Yasuo
Ohshima, Koichi
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453040/
https://www.ncbi.nlm.nih.gov/pubmed/28599462
http://dx.doi.org/10.3892/ol.2017.6067
work_keys_str_mv AT ichikawaayako detectionoftaxspecificctlsinlymphnodesofadulttcellleukemialymphomapatientsanditsassociationwithfoxp3positivityofregulatorytcellfunction
AT miyoshihiroaki detectionoftaxspecificctlsinlymphnodesofadulttcellleukemialymphomapatientsanditsassociationwithfoxp3positivityofregulatorytcellfunction
AT arakawafumiko detectionoftaxspecificctlsinlymphnodesofadulttcellleukemialymphomapatientsanditsassociationwithfoxp3positivityofregulatorytcellfunction
AT kiyasujunichi detectionoftaxspecificctlsinlymphnodesofadulttcellleukemialymphomapatientsanditsassociationwithfoxp3positivityofregulatorytcellfunction
AT satokensaku detectionoftaxspecificctlsinlymphnodesofadulttcellleukemialymphomapatientsanditsassociationwithfoxp3positivityofregulatorytcellfunction
AT niinodaisuke detectionoftaxspecificctlsinlymphnodesofadulttcellleukemialymphomapatientsanditsassociationwithfoxp3positivityofregulatorytcellfunction
AT kimurayoshizo detectionoftaxspecificctlsinlymphnodesofadulttcellleukemialymphomapatientsanditsassociationwithfoxp3positivityofregulatorytcellfunction
AT yoshidamaki detectionoftaxspecificctlsinlymphnodesofadulttcellleukemialymphomapatientsanditsassociationwithfoxp3positivityofregulatorytcellfunction
AT kawanoriko detectionoftaxspecificctlsinlymphnodesofadulttcellleukemialymphomapatientsanditsassociationwithfoxp3positivityofregulatorytcellfunction
AT mutahiroko detectionoftaxspecificctlsinlymphnodesofadulttcellleukemialymphomapatientsanditsassociationwithfoxp3positivityofregulatorytcellfunction
AT sugitayasuo detectionoftaxspecificctlsinlymphnodesofadulttcellleukemialymphomapatientsanditsassociationwithfoxp3positivityofregulatorytcellfunction
AT ohshimakoichi detectionoftaxspecificctlsinlymphnodesofadulttcellleukemialymphomapatientsanditsassociationwithfoxp3positivityofregulatorytcellfunction