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Dissection of the CMV specific T-cell response is required for optimized cardiac transplant monitoring.

Abstract：

:Despite the success of antivirals in preventing clinically overt CMV disease in cardiac allograft recipients, sub-clinical active CMV infection remains a major concern because of its association with allograft rejection and vasculopathy. The measurement of CMV specific T-cell responses is a promising approach to assessing this situation. For simplicity, class-I MHC/peptide-multimers staining CD8 T-cells directly are often used but this ignores a much wider range of responses including the whole CD4 T-cell compartment. CD4 T-cells, however, were recently shown to be critical to reducing CMV load early after transplantation. To determine how extensive T-cell responses to CMV are, the responses to two dominant CMV proteins, IE-1 and pp65, were dissected in detail accounting for T-cell lineage, frequencies, epitope recognition and changes over time in more than 25 heart transplant recipients. Cross-sectional results from over 30 healthy CMV-carriers were analyzed for comparison. Responses were unexpectedly complex, with considerable inter-individual variation in terms of dominance, breadth, and recognized epitopes. Whereas the use of MHC/peptide-multimers for clinical CD8 T-cell response monitoring alone can be justified in some situations, short term T-cell activation combined with intracellular cytokine staining was clearly found to be of more general usefulness. The performance of IFN-gamma, TNF-alpha, or IL-2 as single read-outs in identifying activated T-cells was examined and confirmed that the frequently used IFN-gamma was best suited. These results should be used to inform the design of clinically applicable and diagnostically useful approaches to monitoring CMV specific responses in heart transplant recipients.

journal_name

J Med Virol

journal_title

Journal of medical virology

authors

Kirchner A,Hoffmeister B,Cherepnev-G G,Fuhrmann S,Streitz M,Lachmann R,Bunde T,Meij P,Schönemann C,Hetzer R,Lehmkuhl HB,Volkmer-Engert R,Volk HD,Gratama JW,Kern F

doi

10.1002/jmv.21229

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

1604-14

issue

eissn

0146-6615

issn

1096-9071

journal_volume

pub_type

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Dissection of the CMV specific T-cell response is required for optimized cardiac transplant monitoring.