@article{366046a7d4f044a1be462eb0c515c1d4,
title = "Quantitative Assessment of T Cell Clonotypes in Human Acute Graft-versus-Host Disease Tissues",
abstract = "Owing to the difficulty in isolating T cells from human biopsy samples, the characteristics of T cells that are infiltratinghuman acute graft-versus-host disease (GVHD) tissues remain largely uninvestigated. In the present study, TCR-β deep sequencing of various GVHD tissue samples and concurrent peripheral blood obtained from transplant recipients was performed in combination with functional assays of tissue-infiltrating T cell clones. The T cell repertoire was more skewed in GVHD tissues than in the peripheral blood. The frequent clonotypes differed from tissue to tissue in the same patient, and the frequent clonotypes in the same tissue differed from patient to patient. Two T cell clones were successfully isolated from GVHD skin of a patient. In a cytotoxicity assay, both Tcell clones lysed patient peripheral blood mononuclear cells, but not donor-derived Epstein-Barr virus-transformed lymphoblastoid cells. Their clonotypes were identical to the most and second most frequent T cell clonotypes in the original GVHD skin and accounted for almost all of the skin-infiltrating T cells. These results suggest that human acute GVHD may result from only a few different alloreactive cytotoxic T cell clones, which differ from tissue to tissue and from patient to patient. The characterization of T cells infiltrating human GVHD tissues should be further investigated.",
keywords = "Cytotoxic T cell, Graft-versus-host disease, T cell repertoire, Transplantation",
author = "Daisuke Koyama and Makoto Murata and Ryo Hanajiri and Tomohiro Akashi and Shingo Okuno and Sonoko Kamoshita and Jakrawadee Julamanee and Erina Takagi and Kotaro Miyao and Reona Sakemura and Tatsunori Goto and Seitaro Terakura and Tetsuya Nishida and Hitoshi Kiyoi",
note = "Funding Information: Financial disclosure: This study was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (KAKENHI; 15K09498 and 18K08321, to M.M.), a Practical Research Project for Allergic Diseases and Immunology from the Japan Agency for Medical Research and Development (18ek0510022h0002, to M.M.), and a grant-in-aid from the 24th General Assembly of the Japanese Association of Medical Sciences (to M.M.). Funding Information: The authors thank Chika Wakamatsu, Yoko Matsuyama, and Yasutomo Itoh for their technical assistance. The authors also express their sincere appreciation for experimental and administrative support from the Radioisotope Research Center, Nagoya University Graduate School of Medicine, and the Division of Medical Research Engineering, Nagoya University Graduate School of Medicine. Financial disclosure: This study was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (KAKENHI; 15K09498 and 18K08321, to M.M.), a Practical Research Project for Allergic Diseases and Immunology from the Japan Agency for Medical Research and Development (18ek0510022h0002, to M.M.), and a grant-in-aid from the 24th General Assembly of the Japanese Association of Medical Sciences (to M.M.). Conflict of interest statement: H.K. has received research funding from Chugai Pharmaceutical, Bristol-Myers Squibb, Kyowa Hakko Kirin, Zenyaku Kogyo, FUJIFILM, Nippon Boehringer Ingelheim, Astellas Pharma, and Celgene; consulting fees from Astellas Pharma and Daiichi Sankyo; and honoraria from Bristol-Myers Squibb and Pfizer Japan. These companies were not directly involved in any aspect of the present study. The remaining authors have no conflicts to report. Authorship statement: D.K. and M.M. designed and performed experiments, analyzed the data, and wrote the manuscript. R.H. and T.A. performed experiments and assisted with data analysis. S.O. S.K. J.J. E.T. K.M. R.S. T.G. S.T. and T.N. contributed to the study design and data collection. H.K. supervised the project. All authors read and approved the final manuscript. Financial disclosure: See Acknowledgments on page 423. Publisher Copyright: {\textcopyright} 2018 American Society for Blood and Marrow Transplantation",
year = "2019",
month = mar,
doi = "10.1016/j.bbmt.2018.10.012",
language = "English (US)",
volume = "25",
pages = "417--423",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "3",
}