Protection from cytomegalovirus after transplantation is correlated with immediate early 1-specific CD8 T cells.
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.
Bunde
Torsten
T
Institut für Medizinische Immunologie, Charité, Universitätsmedizin Berlin, Campus Mitte, 10098 Berlin, Germany.
Kirchner
Alexander
A
Hoffmeister
Bodo
B
Habedank
Dirk
D
Hetzer
Roland
R
Cherepnev
Georgy
G
Proesch
Susanna
S
Reinke
Petra
P
Volk
Hans-Dieter
HD
Lehmkuhl
Hans
H
Kern
Florian
F
D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D018604:Epitope Mapping; D005260:Female; D005434:Flow Cytometry; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology*; D012372:ROC Curve; D012307:Risk Factors; D018709:Statistics, Nonparametric; D014180:Transplantation; D014763:Viral Matrix Proteins / Q000276:immunology*
D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; C072628:herpes simplex virus IE3 protein, Human herpesvirus 1; D007371:Interferon-gamma