IntroductionHuman cytomegalovirus (HCMV) infection represents a major clinical problem in immunocompromised persons, including transplant recipients and AIDS patients. Prevalence of HCMV seropositivity ranges between 50% and 90% in healthy adults; after primary infection, the virus establishes lifelong latency in the host. 1 Usually, CMV in immunocompromised patients is caused by the reactivation of latent virus. A number of studies have suggested that the virus may aggravate immunodeficiency by interfering with antigen presentation. [2][3][4][5][6][7] In these publications, dendritic cells (DCs) have been generated from monocytes or CD34 ϩ bone marrow progenitor cells after 5 to 12 days of cytokine-supplemented culture. Such monocyte-derived DCs (moDCs) or bone marrowderived Langerhans cells are highly potent stimulators of T-cell activation. Exposure of these DCs to HCMV leads to functional paralysis of the cells, causing impaired T-cell activation. [2][3][4][5][6][7] Several mechanisms for this immunosuppression have been suggested. First, major histocompatibility complex (MHC) class I and class II and costimulatory molecules are down-regulated, resulting in impaired antigen presentation and increased susceptibility to natural killer cell-mediated lysis. [2][3][4][5][6][7][8] Second, a virally induced, soluble immunosuppressive factor released by mature moDCs has been postulated by several groups and was recently identified as CD83. 5,7 Third, infection of immature moDCs is lytic and leads to cell death. 7 Studies of HCMV effects on moDCs and Langerhans cells have shed light on mechanisms for viral immune evasion. However, the results showing paralysis of antigen presentation also raise questions as to how HCMV can be so effectively controlled in the immunocompetent host. Most primary infections induce minimal symptoms, and there is no clear evidence for clinically relevant immunosuppression. 1 Reactivation of the latent virus is believed to happen frequently, 9,10 but it proceeds asymptomatically in a healthy host, indicating a successful immune response. Indeed, an impressively large part of the T-cell repertoire is HCMV specific in seropositive persons. Labeling with MHC class I tetramers in complex with HCMV peptides has shown that 1% to 4% of all CD8 ϩ T cells are specific for HCMV proteins. 11,12 In view of the low pathogenicity of HCMV in immunocompetent persons, paralysis of key antigen-presenting cells by the virus seems unlikely.Elegant studies in mice have elucidated mechanisms for successful immunity to murine CMV (MCMV). 13 After injection of virus into mice, a small subset of DCs, termed plasmacytoid dendritic cells (PDCs), produce high levels of IFN-␣, IL-12, and TNF-␣. The rapid innate response is followed by maturation of several welldefined DC subsets in the mouse spleen and initiation of a strong MCMV-directed T-cell response. Frequencies of infected DCs were generally low and were restricted to a subset expressing CD8␣. These results show a high degree of specialization between murine DCs ...