DEVELOPMENT OF IMMUNOLOGICAL ASSAYS TO MONITOR PULMONARY ALLOGRAFT-REJECTION

Background - At present the diagnosis of pulmonary allograft rejection is made after examination of transbronchial biopsy specimens; this me thod is highly invasive. A study was performed to determine whether im munological parameters measured in peripheral blood or bronchoalveolar lavage samples correlate with the histological diagnosis of rejection . Methods - Left unilateral pulmonary allotransplantation was performe d between dogs. The animals were immunosuppressed with cyclosporin A a fter transplantation but the dose of this drug was gradually reduced t o allow controlled rejection to take place. Rejection was diagnosed hi stologically. Four immunological parameters were investigated: measure ment of lavage derived T cell proliferation in response to limited cul ture with interleukin 2; measurement of changes in the frequency of do nor reactive cytotoxic T lymphocytes; assay of the level of donor cell binding IgG antibody in recipient plasma; and measurement of the anti body dependent cell mediated cytotoxic response to donor cells after l abelling with recipient plasma. Results - Assays based on measurement of the function of T cells produced significant results at a time late r than the histological diagnosis of severe rejection. The level of do nor reactive IgG antibody increased at a time that corresponded closel y with the diagnosis of severe rejection. This IgG did not activate th e antibody dependent cell mediated cytotoxic effector mechanism to a s ignificant extent. Conclusions - Measurement of parameters of donor sp ecific immunoreactivity can yield data which are indicative of severe pulmonary allograft rejection. These methods make use of samples which can be obtained by minimally invasive methods. Measurement of the pla sma level of donor reactive IgG antibody appears to be the most useful assay. However, each of the in vitro assays used during this series o f experiments was less sensitive to the onset of rejection than was ro utine histological examination.