Hirokawa M, Matsutani T, Saitoh H, Ichikawa Y, Kawabata Y, Horiuchi T, Kitabayashi A, Yoshioka T, Tsuruta Y, Suzuki R, Miura A B, Sawada K
Department of Internal Medicine III, Akita University School of Medicine, Akita, Japan.
Bone Marrow Transplant. 2002 Dec;30(12):915-23. doi: 10.1038/sj.bmt.1703730.
Acute graft-versus-host disease (GVHD) is a disorder involving the skin, gut and liver that is caused by mismatches of major and/or minor histocompatibility antigens between the HLA-identical donor and recipient. If T lymphocytes infiltrating GVHD lesions recognize antigens expressed in these organs, T cell clones should expand in inflammatory tissues. We previously reported that recipients of allogeneic bone marrow grafts have clonally expanded TCRalphabeta(+) T lymphocytes soon after transplantation, which leads to a skew of TCR repertoires. To establish whether or not the same antigens cause clonal expansion of T lymphocytes in both blood and GVHD tissues, we examined the usage of TCR alpha and beta chain variable regions (TCRAV and TCRBV) and determined the complementarity-determining region 3 (CDR3) of T lymphocytes clonally expanded in circulating blood and GVHD lesions. We found that the repertoires and CDR3 diversity of TCRAV and TCRBV differed between the GVHD lesions and circulating blood, suggesting the selective recruitment of antigen-specific T cells into GVHD tissues. We also found that the usage of TCRAV and TCRBV by the clonally expanded T lymphocytes and their CDR3 sequences differed between the GVHD tissues and blood. These results suggest that the antigen specificity of TCRalphabeta(+) T lymphocytes clonally expanded in blood and GVHD lesions is different.
急性移植物抗宿主病（GVHD）是一种累及皮肤、肠道和肝脏的疾病，由HLA配型相同的供体与受体之间主要和/或次要组织相容性抗原不匹配所致。如果浸润GVHD病变部位的T淋巴细胞识别这些器官中表达的抗原，T细胞克隆应在炎症组织中扩增。我们之前报道过，同种异体骨髓移植受者在移植后不久就有克隆性扩增的TCRαβ(+) T淋巴细胞，这导致TCR库出现偏差。为了确定相同抗原是否会导致血液和GVHD组织中的T淋巴细胞克隆性扩增，我们检测了T淋巴细胞受体α和β链可变区（TCRAV和TCRBV）的使用情况，并确定了在循环血液和GVHD病变中克隆性扩增的T淋巴细胞的互补决定区3（CDR3）。我们发现，GVHD病变组织和循环血液中TCRAV和TCRBV的库以及CDR3多样性存在差异，这表明抗原特异性T细胞被选择性募集到GVHD组织中。我们还发现，克隆性扩增的T淋巴细胞对TCRAV和TCRBV的使用及其CDR3序列在GVHD组织和血液之间也有所不同。这些结果表明，在血液和GVHD病变中克隆性扩增的TCRαβ(+) T淋巴细胞的抗原特异性是不同的。
