title: CD28/B7-mediated co-stimulation is critical for early control of murine cytomegalovirus infection.
abstract: Control of acute murine cytomegalovirus (MCMV) infection is dependent upon both innate and adaptive immune responses, relying primarily upon natural killer (NK) and T-cell responses for control. Although CD28/B7 plays a clear role in T-cell responses in many antigen systems including some viral infections, the importance of co-stimulation during MCMV infection is unconfirmed. In addition, recent data suggest that CD28/B7 co-stimulation might also be important to Ly49H+ NK-cell expansion. We therefore hypothesized that CD28/B7 co-stimulation is critical to viral control after MCMV infection, and further that CD28/B7 co-stimulation plays a role in MCMV-specific T- and NK-cell responses. To test these hypotheses, we utilized C57BL/6 mice lacking the co-stimulatory molecules B7-1 and B7-2 or CD28. After primary infection with MCMV, viral titers are significantly elevated in mice lacking CD28 or B7 compared with wild-type mice. Impaired viral control is associated with significant defects in peripheral T-cell responses to MCMV, which appear to be dependent upon CD28/B7 co-stimulation. Abnormal hepatic T-cell responses in CD28(-/-) mice are preceded by impaired MCMV-specific Ly49H+ NK-cell responses. Cytokine evaluations confirm that CD28/B7 co-stimulation is not required for non-specific antiviral responses. We conclude that CD28-mediated co-stimulation is critical for early viral control during acute MCMV infection.
authors.affiliation: Department of Surgery, Ohio State University Medical College, Columbus, Ohio 43210, USA. charles.cook@osumc.edu
authors.forename: Charles H
authors.initials: CH
authors.lastname: Cook
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: Wen
authors.forename: Peter
authors.initials: P
authors.lastname: Zimmerman
authors.forename: Yingxue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Joanne
authors.initials: J
authors.lastname: Trgovcich
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Gao