PMID- 28599462 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1792-1074 (Print) IS - 1792-1082 (Electronic) IS - 1792-1074 (Linking) VI - 13 IP - 6 DP - 2017 Jun TI - 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. PG - 4611-4618 LID - 10.3892/ol.2017.6067 [doi] AB - 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 gamma and HLA-A24 in frozen sections. In addition, the staining of Tax-specific CTLs (HLA-A24-restricted) was analyzed by MHC Dextramer((R)) 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. FAU - Ichikawa, Ayako AU - Ichikawa A AD - Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830 0011, Japan. FAU - Miyoshi, Hiroaki AU - Miyoshi H AD - Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830 0011, Japan. FAU - Arakawa, Fumiko AU - Arakawa F AD - Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830 0011, Japan. FAU - Kiyasu, Junichi AU - Kiyasu J AD - Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830 0011, Japan. FAU - Sato, Kensaku AU - Sato K AD - Biostatistics Center, School of Medicine, Kurume University, Kurume, Fukuoka 830 0011, Japan. FAU - Niino, Daisuke AU - Niino D AD - Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830 0011, Japan. FAU - Kimura, Yoshizo AU - Kimura Y AD - Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830 0011, Japan. FAU - Yoshida, Maki AU - Yoshida M AD - Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830 0011, Japan. FAU - Kawano, Riko AU - Kawano R AD - Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830 0011, Japan. FAU - Muta, Hiroko AU - Muta H AD - Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830 0011, Japan. FAU - Sugita, Yasuo AU - Sugita Y AD - Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830 0011, Japan. FAU - Ohshima, Koichi AU - Ohshima K AD - Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830 0011, Japan. LA - eng PT - Journal Article DEP - 20170421 PL - Greece TA - Oncol Lett JT - Oncology letters JID - 101531236 PMC - PMC5453040 OTO - NOTNLM OT - Foxp3 OT - Tax-specific cytotoxic T-cell OT - adult T-cell leukemia/lymphoma OT - human T-cell lymphotropic virus OT - regulatory T-cell EDAT- 2017/06/11 06:00 MHDA- 2017/06/11 06:01 PMCR- 2017/04/21 CRDT- 2017/06/11 06:00 PHST- 2015/05/12 00:00 [received] PHST- 2016/09/27 00:00 [accepted] PHST- 2017/06/11 06:00 [entrez] PHST- 2017/06/11 06:00 [pubmed] PHST- 2017/06/11 06:01 [medline] PHST- 2017/04/21 00:00 [pmc-release] AID - OL-0-0-6067 [pii] AID - 10.3892/ol.2017.6067 [doi] PST - ppublish SO - Oncol Lett. 2017 Jun;13(6):4611-4618. doi: 10.3892/ol.2017.6067. Epub 2017 Apr 21.