Immune cells and immunosuppression in a porcine bronchial model of obliterative bronchiolitis

Background. To study obliterative bronchiolitis (OB), we have developed a p orcine heterotopic bronchial model. Allografts obliterate within 3 weeks, t he immunosuppression cyclosporine (CsA)-azathioprine (AZA)-methylprednisolo ne (MP) delays OB, but OB is prevented when AZA is switched to 40-0-(2-hydr oxy-ethyl)-rapamycin (RAD). To characterize our model, we studied immune ce lls under various immunosuppressive conditions. Methods. The groups studied were autografts (U), allografts (A), and allogr afts given either CsA-RAD-MP (R), or CsA-AZA-MP (C). The implants were harv ested at 3, 7, 10, 14, 21, 30, 60, and 90 days after transplantation. Epith elial damage and obliteration were graded histologically, and the number of CD4, CD8, MHC class II expressing cells, macrophages, and B lymphocytes we re counted (mean + SEM)/high-power visual field. Results. In group U, normal epithelium was regained with no obliteration an d only few immune cells. In group A, consistent with initially acute ejecti on, an influx of CD4 (105+23), CD8 (166+23), and class II (92+20) cells was seen up to day 21, when total obliteration preceded by epithelial destruct ion had already developed. Some macrophages were seen and B cells were scar ce. In group R, epithelial damage and obliteration were insignificant, but moderate numbers of CD4, CD8, and class II cells were seen. In group C, epi thelial damage and obliteration were only delayed, but the immune cell resp onse was clearly blunted. Conclusions. In our model, rejection with significant immune cell influx wa s still active when obliteration was total in nontreated allografts. In imm unosuppressed allografts, decrease in the number of immune cells alone did prevent OB. These results support OB being T-cell mediated. RAD may have ad ditional important effects on growth factors and proliferation in preventio n of OB.