title: CCL8 and the Immune Control of Cytomegalovirus in Organ Transplant Recipients.
abstract: Monitoring of cytomegalovirus cell-mediated immunity is a promising tool for the refinement of preventative and therapeutic strategies posttransplantation. Typically, the interferon-γ response to T cell stimulation is measured. We evaluated a broad range of cytokine and chemokines to better characterize the ex vivo host-response to CMV peptide stimulation. In a cohort of CMV viremic organ transplant recipients, chemokine expression-specifically CCL8 (AUC 0.849 95% CI 0.721-0.978; p = 0.003) and CXCL10 (AUC 0.841, 95% CI 0.707-0.974; p = 0.004)-was associated with control of viral replication. In a second cohort of transplant recipients at high-risk for CMV, the presence of a polymorphism in the CCL8 promoter conferred an increased risk of viral replication after discontinuation of antiviral prophylaxis (logrank hazard ratio 3.6; 95% CI 2.077-51.88). Using cell-sorting experiments, we determined that the primary cell type producing CCL8 in response to CMV peptide stimulation was the monocyte fraction. Finally, in vitro experiments using standard immunosuppressive agents demonstrated a dose-dependent reduction in CCL8 production. Chemokines appear to be important elements of the cell-mediated response to CMV infection posttransplant, as here suggested for CCL8, and translation of this knowledge may allow for the tailoring and improvement of preventative strategies.
authors.affiliation: Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: L F
authors.initials: LF
authors.lastname: Lisboa
authors.affiliation: Infection Biology Lab, Department Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Egli
authors.affiliation: Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Fairbanks
authors.affiliation: Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: D
authors.initials: D
authors.lastname: O'Shea
authors.affiliation: Infectious Diseases Service and Transplantation Center, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
authors.forename: O
authors.initials: O
authors.lastname: Manuel
authors.affiliation: Department of Medicine and Multi-organ Transplant Program, University Health Network, Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Husain
authors.affiliation: Department of Medicine and Multi-organ Transplant Program, University Health Network, Toronto, Ontario, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Department of Medicine and Multi-organ Transplant Program, University Health Network, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Humar
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D054412:Chemokine CCL8 / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003587:Cytomegalovirus / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D005500:Follow-Up Studies; D005805:Genes, MHC Class I / Q000276:immunology; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy; D016377:Organ Transplantation; D010446:Peptide Fragments / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011183:Postoperative Complications; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D066027:Transplant Recipients; D014766:Viremia / Q000453:epidemiology / Q000276:immunology* / Q000401:mortality; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D054412:Chemokine CCL8; D016207:Cytokines; D010446:Peptide Fragments
keywords: chemokines / chemokine receptors; immunobiology; infection and infectious agents; infectious disease; translational research / science; viral: Cytomegalovirus (CMV)