Cytotoxic T lymphocytes directed against donor HLA class I antigens on airway epithelial cells are present in bronchoalveolar lavage fluid from lung transplant recipients during acute rejection

Background: The lung epithelium is among the first donor tissues encountere d by the lung allograft recipient's immune system. The purpose of this stud y was to determine whether lung epithelium was recognized by T lymphocytes that are isolated from bronchoalveolar lavage fluid of lung allograft recip ients during periods of acute rejection. Methods: Lymphocytes isolated from 45 bronchoalveolar lavage samples (from 41 lung transplant recipients) ser ved as effector cells in standard cell-mediated cytolytic assays with sever al cell lines as targets: BEAS-2B (an immortalized airway epithelial cell l ine); B-lymphoblastoid cell lines; and K562 (a natural killer-sensitive cel l line), Cytotoxic T-lymphocyte activity of bronchoalveolar lavage lymphocy tes was correlated with pathologic status. Results: During acute rejection alone (ie, without concomitant cytomegalovirus infection), mean lysis of th e airway epithelial target was significantly greater, compared with during no rejection, when these targets expressed donor-specific HLA class I antig ens (P =.007). Lysis of donor class I-matched B-lymphoblastoid cell line ta rgets during rejection was not significantly different from lysis during no -rejection periods (P =.18). Mean lysis of K562, a natural killer cell targ et, did not differ between acute rejection (without concomitant cytomegalov irus infection) and no rejection (P =.30), During cytomegalovirus infection (without concomitant acute rejection), there was no difference in mean lys is of airway epithelial cells, B-lymphoblastoid cell lines, or K562 targets compared with during no cytomegalovirus infection, whereas during acute re jection, compared with cytomegalovirus infection without rejection, there w as a significant increase in mean lysis of the airway epithelial target whe n it expressed donor-specific HLA antigens (P =.01). Conclusions: Donor HLA class I-specific cytotoxic T-lymphocyte activity directed at airway epithe lial cells was demonstrated in bronchoalveolar lavage lymphocytes from lung transplant recipients, Lysis of these targets was significantly higher dur ing episodes of acute rejection.