LECTIN-DEPENDENT CELL-MEDIATED CYTOTOXICITY AND NATURAL-KILLER FUNCTION IN REJECTING AND INFECTED LUNG ALLOGRAFTS

Differentiation between rejection and infection of lung allografts rem ains difficult. The effects of these two pathologic entities on the cy tolytic activity of bronchoalveolar lavage (BAL) and PBL were investig ated. Left lung allotransplantation was performed on 16 mongrel dogs o f which 12 were available for complete studies. All animals received C A, AZA, and PRED for 2 weeks. Four grafts developed left lower lobe Gr am negative pneumonia. The eight remaining recipients progressed gradu ally to severe rejection after acute reduction of immunosuppression. C ytolytic activity of blood and left lung BAL lymphocytes was quantitat ed by the natural killer (NK) and lectin-dependent cell-mediated cytot oxicity (LDCMC) assays. Two additional groups serving as controls were either given a 10-day course of immunosuppressants or had right lower lobe pneumonia induced by transbronchial inoculation of gram negative bacteria. Immunosuppressed control animals showed significant depress ion of PBL and BAL lymphocyte LDCMC and NK activity. Similarly, BAL ly mphocytes expressed very low LDCMC in normal allografts (2.8+/-0.8%). Once rejection developed and progressed, LDCMC became significantly hi gher (15.6+/-2.2 and 52.7+/-2.8% in mild and severe rejection, respect ively). There was no detectable NK activity in rejecting lung allograf ts. BAL lymphocytes from infected allografts, on the other hand, showe d an elevation of both NK and LDCMC activity (9.1+/-1.1 and 14.6+/-1.0 %, respectively). Similarly, bacterial pneumonia in control animals ma nifested an increase in NK and LDCMC activity in lung and blood. PBL l ymphocytes of lung allograft recipients, however, had increased NK and LDCMC activity in both rejection and infection. LDCMC/NK activity rat io (LM/NK index) of lung lymphocytes was significantly higher in rejec ting allografts (11.2+/-1.0 and 12.4+/-1.6 for mild and severe rejecti on, respectively) than in infected ones (1.2+/-0.3, P<0.0001). It appe ars, from this study, that rejection of the lung allograft results in alterations in BAL lymphocyte phenotypes and functions that differ fro m those associated with bacterial infection. Such differences may be u seful in distinguishing episodes of acute allograft rejection from bac terial infection.