RT Journal Article
SR Electronic
T1 Development of immunological assays to monitor pulmonary allograft rejection.
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 151
OP 156
DO 10.1136/thx.49.2.151
VO 49
IS 2
A1 A C Cunningham
A1 J A Kirby
A1 I W Colquhoun
A1 P A Flecknell
A1 T Ashcroft
A1 J H Dark
YR 1994
UL http://thorax.bmj.com/content/49/2/151.abstract
AB BACKGROUND--At present the diagnosis of pulmonary allograft rejection is made after examination of transbronchial biopsy specimens; this method is highly invasive. A study was performed to determine whether immunological parameters measured in peripheral blood or bronchoalveolar lavage samples correlate with the histological diagnosis of rejection. METHODS--Left unilateral pulmonary allotransplantation was performed between dogs. The animals were immunosuppressed with cyclosporin A after transplantation but the dose of this drug was gradually reduced to allow controlled rejection to take place. Rejection was diagnosed histologically. Four immunological parameters were investigated: measurement of lavage derived T cell proliferation in response to limited culture with interleukin 2; measurement of changes in the frequency of donor reactive cytotoxic T lymphocytes; assay of the level of donor cell binding IgG antibody in recipient plasma; and measurement of the antibody dependent cell mediated cytotoxic response to donor cells after labelling with recipient plasma. RESULTS--Assays based on measurement of the function of T cells produced significant results at a time later than the histological diagnosis of severe rejection. The level of donor reactive IgG antibody increased at a time that corresponded closely with the diagnosis of severe rejection. This IgG did not activate the antibody dependent cell mediated cytotoxic effector mechanism to a significant extent. CONCLUSIONS--Measurement of parameters of donor specific 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 plasma level of donor reactive IgG antibody appears to be the most useful assay. However, each of the in vitro assays used during this series of experiments was less sensitive to the onset of rejection than was routine histological examination.