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Immune Reconstitution

Distinct TCRAV and TCRBV repertoire and CDR3 sequence of T lymphocytes clonally expanded in blood and GVHD lesions after human allogeneic bone marrow transplantation

Bone Marrow Transplantation volume 30, pages 915–923 (2002)Cite this article

Abstract

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 TCRαβ+ 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 α and β 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 TCRαβ+ T lymphocytes clonally expanded in blood and GVHD lesions is different.

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Acknowledgements

We thank Dr Setsuya Ohtani for performing diagnostic colonofiberscopic examinations. This work was supported by grants from the Ministry of Education, Science, Sports and Culture of Japan (08670508, 10670932 and 14570960), the Yamashita Taro-Kensho Memorial Foundation and the Uehara Memorial Foundation.

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Authors and Affiliations

  1. Department of Internal Medicine III, Akita University School of Medicine, Akita, Japan

    M Hirokawa, H Saitoh, Y Ichikawa, Y Kawabata, T Horiuchi, A Kitabayashi, AB Miura & K Sawada

  2. Department of Immunology, Shionogi Institute for Medical Science, Osaka, Japan

    T Matsutani, T Yoshioka, Y Tsuruta & R Suzuki

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  1. M Hirokawa
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Hirokawa, M., Matsutani, T., Saitoh, H. et al. Distinct TCRAV and TCRBV repertoire and CDR3 sequence of T lymphocytes clonally expanded in blood and GVHD lesions after human allogeneic bone marrow transplantation. Bone Marrow Transplant 30, 915–923 (2002). https://doi.org/10.1038/sj.bmt.1703730

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