Effect of CTLA4-Ig on obliterative bronchiolitis in a mouse intrapulmonary tracheal transplantation model
Annals of Thoracic and Cardiovascular Surgery, 2021•jstage.jst.go.jp
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 …
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 …
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.
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