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Our previous study suggested that hypomethylation of perforin promoter of CD4 + T cells might be involved in the pathogenesis of autoimmune emphysema of rats. Whether transfer of this kind of cells hypomethylated  in vitro  into naive immunocompetent rats also results in emphysema is unknown yet. To test the hypothesis above, thirty Sprague Dawley (SD) rats were randomly divided into three groups: a model group ( n  = 10), a normal control group ( n  = 10) and a sham operation group ( n  = 10). In the model group, spleen-derived CD4 + T cells of normal rats were treated with 5-azacytidine (5-Aza), complete Freund’s adjuvant and Phosphate Buffered Saline (PBS), then transferred into naive immunocompetent rats. The normal control group was injected with CD4 + T lymphocytes from spleens of normal rats and the same amount of adjuvant and PBS as above. In sham operation group, normal rats were injected intraperitoneally with complete Freund’s adjuvant and PBS. Histopathological evaluations (mean linear Intercept (MLI) and mean alveolar numbers (MAN)), anti-endothelial cell antibodies (AECA) in serum and bronchoalveolar lavage fluid (BALF), lung vascular endothelial growth factor (VEGF)), the apoptotic index (AI) of alveolar septal cells and the methylation levels of perforin promoter of CD4 + T cells were investigated. The levels of the methylation above and MAN were lower in the model group than in the control and the sham operation group, while the AECA in serum and BALF, VEGF, MLI and the AI were greater (all  p  &lt; 0.05). The methylation levels of perforin promoter were positively correlated with the MAN ( r  = 0.747,  p  &lt; 0.05) and negatively correlated with AI, AECA, MLI, and VEGF ( r  was −0.789, −0.746, −0.743, −0.660, respectively, all  p  &lt; 0.05). This study suggests that transfer of invitro CD4 + T cells with hypomethylation of perforin promoter into rats causes autoimmune emphysema, possibly by increasing expression of VEGF and promoting alveolar septal cell apoptosis.

Transfer of Invitro CD4 + T Cells with Hypomethylation of Perforin Promoter into Rats’ Abdomens Causes Autoimmune Emphysema