title: Protection from cytomegalovirus after transplantation is correlated with immediate early 1-specific CD8 T cells.
abstract: 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.
authors.affiliation: Institut für Medizinische Immunologie, Charité, Universitätsmedizin Berlin, Campus Mitte, 10098 Berlin, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Bunde
authors.forename: Alexander
authors.initials: A
authors.lastname: Kirchner
authors.forename: Bodo
authors.initials: B
authors.lastname: Hoffmeister
authors.forename: Dirk
authors.initials: D
authors.lastname: Habedank
authors.forename: Roland
authors.initials: R
authors.lastname: Hetzer
authors.forename: Georgy
authors.initials: G
authors.lastname: Cherepnev
authors.forename: Susanna
authors.initials: S
authors.lastname: Proesch
authors.forename: Petra
authors.initials: P
authors.lastname: Reinke
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Hans
authors.initials: H
authors.lastname: Lehmkuhl
authors.forename: Florian
authors.initials: F
authors.lastname: Kern
mesh_terms: 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*
chemical_list: 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