Quantitative assessment of TCR repertoire and allo-reactivity of human acute GVHD tissue-infiltrating T cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09498
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Nagoya University
• Principal Investigator: Murata Makoto 名古屋大学, 医学系研究科, 准教授 (40378063)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 造血幹細胞移植 / 移植片対宿主病 / T細胞 / 抗原 / HLA

Outline of Final Research Achievements

T cell repertoire was extremely skewed in human acute GVHD tissues. Two allo-reactive cytotoxic T cell clones were isolated from GVHD skin of a patient. Interestingly, their clonotypes were identical to the most and second most frequent clonotypes in the skin and accounted for almost all of the skin-infiltrating T cells. These results suggest that human acute GVHD can result from a few different allo-reactive cytotoxic T cell clones. In the analysis for 12 acute GVHD tissues, the frequent T cell clonotypes differed from tissue to tissue of the same patient, and the frequent T cell clonotypes in the same tissue differed from patient to patient. Importantly, there was an association between the low 1/Ds of GVHD tissue-infiltrating T cells and poor response to first-line steroid treatment, suggesting that evaluation of the degree of skewing of tissue-infiltrating T cells may allow us to establish a novel biomarker that predicts treatment response.

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