Association of human cytomegalovirus DNA aemia and specific granzyme B responses in lung transplant recipients

Summary In lung transplant recipients ( LTR s), human cytomegalovirus ( HCMV ) DNA aemia could be associated with HCMV disease and reduced allograft survival. In the present study we analysed whether or not HCMV ‐specific granzyme B ( G rz‐ B ) responses indicating CD 8 + T cell cytotoxicity exert an impact on HCMV DNA aemia and relate to specific interferon ( IFN) ‐γ secretion. HCMV ‐specific G rz‐ B responses were quantitated by enzyme‐linked immunosorbent assay ( ELISA) in 70 samples from 39 HCMV seropositive LTR s who were prospectively investigated for HCMV DNA plasma levels and IFN ‐γ kinetics using a standardized CD 8 + T cell assay ( Q uanti FERON ®‐ CMV assay). In all LTR s who were protected from HCMV DNA aemia by early and persistent IFN ‐γ responses, G rz‐ B responses were also detected. In LTR s who developed episodes of HCMV DNA aemia, the G rz‐ B responses which were detected prior to viral DNA detection differed significantly in patients who experienced episodes with high (exceeding 1000 copies/ml) and low plasma DNA levels ( P  = 0·0290, F isher's exact test). Furthermore, the extent of G rz‐ B release prior to viral DNA aemia correlated statistically with the detected levels of IFN ‐γ ( P  < 0·0001, S pearman's rank test). Of note, simultaneous detection of G rz‐ B and IFN ‐γ secretion was associated significantly with protection from high HCMV DNA plasma levels during the subsequent follow‐up ( P  = 0·0057, F isher's exact test), and this association was stronger than for IFN ‐γ detection alone. We conclude that, in addition to IFN ‐γ responses, G rz‐ B secretion by CD 8 + T cells is essential to control HCMV replication and a simultaneous measurement of IFN ‐γ and G rz‐ B could contribute to the immune monitoring of LTR s.