Effect of CTLA4-Ig on Obliterative  Bronchiolitis in a Mouse Intrapulmonary  Tracheal Transplantation Model

Yamato Suzuki; Hisashi Oishi; Masahiko Kanehira; Yasushi Matsuda; Takashi Hirama; Masafumi Noda; Yoshinori Okada

doi:10.5761/atcs.oa.20-00398

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Effect of CTLA4-Ig on Obliterative Bronchiolitis in a Mouse Intrapulmonary Tracheal Transplantation Model

Yamato Suzuki, Hisashi Oishi, Masahiko Kanehira, Yasushi Matsuda, Takashi Hirama, Masafumi Noda, Yoshinori Okada

著者情報

Yamato Suzuki
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan
Hisashi Oishi
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan
Masahiko Kanehira
Center for Life Science Research, University of Yamanashi, Chuo, Yamanashi, Japan
Yasushi Matsuda
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan
Department of Thoracic Surgery, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
Takashi Hirama
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan
Masafumi Noda
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan
Yoshinori Okada
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan

キーワード: lung transplantation, chronic lung allograft dysfunction, obliterative bronchiolitis, cytotoxic T-lymphocyte-associated antigen 4

ジャーナルオープンアクセス早期公開

論文ID: oa.20-00398

DOI https://doi.org/10.5761/atcs.oa.20-00398

この記事には本公開記事があります。

The final version of this article is now available: Vol. 27 (2021), No. 6 pp. 355-365

詳細

抄録

Objectives: One of the serious problems after lung transplantation is chronic lung allograft dysfunction (CLAD). Most CLAD patients pathologically characterized by obliterative bronchiolitis (OB). Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)-Ig is a combination protein of the Fc fragment of human IgG1 linked to the extracellular domain of CTLA4. The aim of the study was to examine the effect of CTLA4-Ig therapy on OB using a mouse intrapulmonary tracheal transplantation (IPTT) model.

Methods: IPTT was performed between BALB/c (donor) and C57BL/6 (recipient) mice. Abatacept, which is a commercially available form of CTLA4-Ig, was intraperitoneally injected in recipient mice immediately after surgery, on days 7, 14, and 21. The mice in the control group received human IgG.

Results: We performed semi-quantitative analysis of graft luminal obliteration at post-transplant day 28. We calculated the obliteration ratio of the lumen of the transplanted trachea in each case. The obliteration ratio was significantly lower in the CTLA4-Ig group than that in the control group (91.2 ± 2.1% vs. 47.8 ± 7.9%, p = 0.0008). Immunofluorescent staining revealed significantly decreased lymphoid neogenesis in the lung.

Conclusions: CTLA4-Ig therapy attenuated tracheal obliteration with fibrous tissue in the mouse IPTT model. The attenuation of fibrous obliteration was correlated with the inhibition of lymphoid neogenesis.

責任著者(Corresponding author)

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