title: Parameters determining the efficacy of adoptive CD8 T-cell therapy of cytomegalovirus infection.
abstract: Reactivation of latent cytomegalovirus (CMV) in the transient state of immunodeficiency after hematopoietic cell transplantation (HCT) is the most frequent and severe viral complication endangering leukemia therapy success. By infecting the bone marrow (BM) stroma of the transplantation recipient, CMV can directly interfere with BM repopulation by the transplanted donor-derived hematopoietic cells and thus delay immune reconstitution of the recipient. Cytopathogenic virus spread in tissues can result in CMV disease with multiple organ manifestations of which interstitial pneumonia is the most feared. There exists a 'window of risk' between hematoablative treatment and reconstitution of antiviral immunity after HCT, whereby timely reconstitution of antiviral CD8 T cells is a recognized positive prognostic parameter for the control of reactivated CMV infection and prevention of CMV disease. Supplementation of endogenous reconstitution by adoptive cell transfer of 'ready-to-go' effector and/or memory virus epitope-specific CD8 T cells is a therapeutic option to bridge the 'window of risk.' Preclinical research in murine models of CMV disease has been pivotal by providing 'proof of concept' for a benefit from CD8 T-cell therapy of HCT-associated CMV disease (reviewed in Holtappels et al. Med Microbiol Immunol 197:125-134, 2008). Here, we give an update of our previous review with focus on parameters that determine the efficacy of adoptive immunotherapy of CMV infection by antiviral CD8 T cells in the murine model.
authors.affiliation: Institute for Virology, University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Strasse 67, Hochhaus am Augustusplatz, 55131 Mainz, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ebert
authors.forename: Jürgen
authors.initials: J
authors.lastname: Podlech
authors.forename: Dorothea
authors.initials: D
authors.lastname: Gillert-Marien
authors.forename: Kerstin M
authors.initials: KM
authors.lastname: Gergely
authors.forename: Julia K
authors.initials: JK
authors.lastname: Büttner
authors.forename: Annette
authors.initials: A
authors.lastname: Fink
authors.forename: Kirsten
authors.initials: K
authors.lastname: Freitag
authors.forename: Doris
authors.initials: D
authors.lastname: Thomas
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Reddehase
authors.forename: Rafaela
authors.initials: R
authors.lastname: Holtappels
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D003586:Cytomegalovirus Infections / Q000628:therapy*; D004195:Disease Models, Animal; D016867:Immunocompromised Host; D051379:Mice; D016896:Treatment Outcome