The early changes of respiratory system resistance and γδT lymphocytes infiltrated in graft after lung transplantation of mouse

Objectives To generate an orthotopic left lung transplantation model in mice, and to observe the early changes of respiratory system resistance and γδT lymphocytes infiltrated in grafts. Methods The research time was from March 2014 to May 2015. The male C57BL/6 mice (n=35) and BALB/c mice (syngenic group, n=10) were randomly divided into five groups. Control group (n=5): wild C57BL/6 mice; syngenic transplant group (n=10): C57BL/6→C57BL/6; allogenic transplant group(allogenic group, n=10): BALB/c→C57BL/6; each transplant group was randomly divided into 3-day and 7-day subgroups (n=5). Respiratory system resistance and histological features of grafts were assessed, and differences in graft infiltrating γδT lymphocytes and mRNA expression of interleukin (IL)-17A were quantified on 3 and 7 days after transplantation. Multiple comparisons were performed using one-way analysis of variance and least significant difference analysis. Results (1) The respiratory system resistance of syngenic group and allogenic group were (2.61±0.59) cmH2O·s/ml and (2.84±0.31) cmH2O·s/ml 3 days post-operation, both of them increased compared to control group (1.39±0.17) cmH2O·s/ml (1 cmH2O=0.098 kPa) (P=0.001, 0.000). The respiratory system resistance of allogenic group were (4.33±0.67) cmH2O·s/ml 7 days post-operation, which was significantly higher than that of syngenic 7-day subgroup (1.87±0.27) cmH2O·s/ml and control group (1.39±0.17) cmH2O·s/ml (P=0.000, 0.000). (2) The isografts of syngenic group showed a relatively normal histological appearance with minimal infiltration of inflammatory cells, and the allografts of allogenic group infiltrated apparently by inflammatory cells, especially 7-day subgroup showed acute cellular rejection. (3) The percentage of γδT lymphocytes infiltrated in isografts and allografts were 3.90%±0.86% and 4.40%±0.57%, respectively, which were significantly increased compared to that of control lungs 2.00%±0.23% 3 days post-operation(P=0.000, 0.000); The percentage of γδT lymphocytes infiltrated in 7 days allografts was 5.40%±0.98% , which was higher compared to that of 7 days isografts 2.60%±0.54% and control lungs 2.00%±0.23% (P=0.000, 0.000). (4) IL-17A mRNA expression levels were 3.37±0.55 and 5.23±1.50 in isografts and 6.77±0.93 and 27.32±4.20 in allografts, on postoperative day 3 and 7 respectively. All of them were significantly upregulated compared to that of control lungs 0.99±0.08 (P=0.000, 0.000), and allografts exhibited significantly greater IL-17A transcript levels compared to isografts on postoperative day 3 and 7 (P=0.000, 0.000). Conclusion The rise of respiratory system resistance of lung grafts after transplantation may relate to the increased IL-17A-producing γδT lymphocytes infiltrated in the grafts. Key words: Lung transplantation; Respiratory function tests; T-lymphocytes; Interleukin-17