Use of a biotinylated DNA probe specific for the human Y chromosome in the evaluation of the allograft lung.

A cloned 3.4 kilobase DNA probe derived from the heterochromatin of the Y chromosome was used to investigate the regeneration and reepithelialization of allograft lungs of nine recipients who received sex mismatched donor organs. Patients were monitored for varying periods of time, up to four years, by transbronchial biopsy. In situ hybridization on paraffin-embedded biopsies utilizing the Y probe revealed that bronchial and alveolar epithelium and arterial and venous endothelium of the peripheral lung retained a donor phenotype, irrespective of episodes of acute or chronic rejection (obliterative bronchiolitis) which are known to injure these cellular subsets. In contrast, migratory cells, lymphocytes and macrophages, gradually, at varying rates, infiltrated the allografted lungs, replacing preexisting donor elements. Cases of active OB were manifested by infiltration of bronchioles by sex-mismatched lymphocytes; however, in some instances, quiescent recipient lymphocytes colonized the allograft and were unassociated with histologic rejection. Macrophages of similar sex seemed to cluster together within air spaces. Use of a DNA probe for the Y chromosome and in situ hybridization techniques allow monitoring of cellular alterations over time in recipients with sex mismatched allografts.