CCL8 and the Immune Control of Cytomegalovirus in Organ Transplant Recipients.
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.
['Lisboa|L F|LF|', 'Egli|A|A|', 'Fairbanks|J|J|', "O'Shea|D|D|", 'Manuel|O|O|', 'Husain|S|S|', 'Kumar|D|D|', 'Humar|A|A|']
D000998:Antiviral Agents D016022:Case-Control Studies D054412:Chemokine CCL8 D015331:Cohort Studies D016207:Cytokines D003587:Cytomegalovirus D003586:Cytomegalovirus Infections D005500:Follow-Up Studies D005805:Genes, MHC Class I D006084:Graft Rejection D006085:Graft Survival D006801:Humans D007111:Immunity, Cellular D007165:Immunosuppression Therapy D016377:Organ Transplantation D010446:Peptide Fragments D020641:Polymorphism, Single Nucleotide D011183:Postoperative Complications D011379:Prognosis D011401:Promoter Regions, Genetic D012307:Risk Factors D015996:Survival Rate D013601:T-Lymphocytes D066027:Transplant Recipients D014766:Viremia D014779:Virus Replication
chemokines / chemokine receptors immunobiology infection and infectious agents infectious disease translational research / science viral: Cytomegalovirus (CMV)