Features of repertoire diversity and gene expression in human cytotoxic T cells following allogeneic hematopoietic cell transplantation

同种异体造血细胞移植后人细胞毒性T细胞库多样性及基因表达特点

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作者:Hideki Nakasone, Machiko Kusuda, Kiriko Terasako-Saito, Koji Kawamura, Yu Akahoshi, Masakatsu Kawamura, Junko Takeshita, Shunto Kawamura, Nozomu Yoshino, Kazuki Yoshimura, Yukiko Misaki, Ayumi Gomyo, Kazuaki Kameda, Masaharu Tamaki, Aki Tanihara, Shun-Ichi Kimura, Shinichi Kako, Yoshinobu Kanda

Abstract

Cytomegalovirus reactivation is still a critical concern following allogeneic hematopoietic cell transplantation, and cellular immune reconstitution of cytomegalovirus-specific cytotoxic T-cells is necessary for the long-term control of cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation. Here we show the features of repertoire diversity and the gene expression profile of HLA-A24 cytomegalovirus-specific cytotoxic T-cells in actual recipients according to the cytomegalovirus reactivation pattern. A skewed preference for BV7 genes and sequential "G" amino acids motif is observed in complementarity-determining region-3 of T cell receptor-β. Increased binding scores are observed in T-cell clones with complementarity-determining region-3 of T cell receptor-β with a "(G)GG" motif. Single-cell RNA-sequence analyses demonstrate the homogenous distribution of the gene expression profile in individual cytomegalovirus-specific cytotoxic T-cells within each recipient. On the other hand, bulk RNA-sequence analyses reveal that gene expression profiles among patients are different according to the cytomegalovirus reactivation pattern, and are associated with cytokine production or cell division. These methods and results can help us to better understand immune reconstitution following hematopoietic cell transplantation, leading to future studies on the clinical application of adoptive T-cell therapies.

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