The Journal of Experimental Medicine
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Published online 28 March 2005 doi:10.1084/jem.20042384
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 7, 1031-1036
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BRIEF DEFINITIVE REPORT

 Protection from cytomegalovirus after transplantation is correlated with immediate early 1–specific CD8 T cells

Torsten Bunde1, Alexander Kirchner1, Bodo Hoffmeister1, Dirk Habedank3, Roland Hetzer3, Georgy Cherepnev1, Susanna Proesch2, Petra Reinke4, Hans-Dieter Volk1, Hans Lehmkuhl3, and Florian Kern1

1 Institut für Medizinische Immunologie, Charité, Universitätsmedizin Berlin, Campus Mitte, 10098 Berlin, Germany
2 Institut für Virologie, Charité, Universitätsmedizin Berlin, Campus Mitte, 10098 Berlin, Germany
3 Deutsches Herzzentrum, 13353 Berlin, Germany
4 Medizinische Klinik mit Schwerpunkt Nephrologie und internistische Intensivmedizin, Charité, Campus Virchow-Klinikum, 13353 Berlin, Germany

CORRESPONDENCE Florian Kern: florian.kern{at}charite.de

T cells are crucial for the control of cytomegalovirus (CMV) in infected individuals. Although CMV-specific T cells can be quantified by various methods, clear correlates of protection from CMV disease have not been defined. However, responses to the pp65 protein are believed to play an important role. Here, the proportions of interferon {gamma}–producing T cells following ex vivo activation with pools of overlapping peptides representing the pp65 and immediate early (IE)-1 proteins were determined at multiple time points and related to the development of CMV disease in 27 heart and lung transplant recipients. Frequencies of IE-1–specific CD8 T cells above 0.2 and 0.4% at day 0 and 2 wk, respectively, or 0.4% at any time during the first months discriminated patients who did not develop CMV disease from patients at risk, 50–60% of whom developed CMV disease. No similar distinction between risk groups was possible based on pp65-specific CD8 or CD4 T cell responses. Remarkably, CMV disease developed exclusively in patients with a dominant pp65-specific CD8 T cell response. In conclusion, high frequencies of IE-1 but not pp65-specific CD8 T cells correlate with protection from CMV disease. These results have important implications for monitoring T cell responses, adoptive cell therapy, and vaccine design.

T. Bunde and A. Kirchner share senior authorship for this work.


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