Experience-Dependent Pathological Variations in Minor-Mismatched Mouse Lung Transplantation

Abstract

<h3>Purpose</h3> Mouse orthotopic single lung transplantation (LTx) is a useful scientific model to explore LTx immunology. C57BL/10 (B10, H-2^b) to C57BL/6 (B6, H-2^b) minor alloantigen-mismatched LTx exhibits mild acute rejection and sometimes chronic fibrosis, mimicking human LTx where alloimmunity is dampened by immunosuppressants. We have observed variations in allograft histology across experiments, which were not explained by animal vendor or experimental conditions. The purpose of this study was to evaluate those variations objectively. <h3>Methods</h3> We performed a retrospective review of B10 to B6 LTx performed in our lab and sacrificed 28 days after LTx. LTx with an experimental intervention (e.g., usage of immunomodulatory agents or knock-out mice) were excluded. Surgeons 1 and 2 had had previous rodent LTx experience whereas Surgeons 3-5 had not. Each surgeon's first 10, middle 10, and last 10 LTx in our lab were pathologically graded in a blinded manner. Nonparametric Spearman correlation was computed to compare chronological variation across surgeons. Inter-surgeon differences were compared using two-way ANOVA. <h3>Results</h3> Data from 143 LTx were available from five surgeons' records. Surgeon 1's and 2's pathology scores were mostly stable throughout the period (e.g. for B-grade rejection, Surgeon 1 r=0.10 and p=0.60, Surgeon 2 r=-0.11 and p=0.55), whereas those of surgeons 3-5 changed over time (e.g. for B-grade rejection, Surgeon 4 r=-0.57 and p<0.01, Surgeon 5 r=0.54 and p<0.01) (Fig 1A). A similar tendency was observed in A-grade rejection and obliterative-airway fibrosis. Each surgeon's trajectory was significantly different from each other (Fig 1B). <h3>Conclusion</h3> Mouse single LTx is a powerful model to study the underlying mechanisms of LTx biology. However, the surgeon- and experience-dependent variability in histopathological findings need to be taken into account when designing experimental protocols, particularly when the model has recently been acquired by the surgeon.