We have developed a novel diagnostic technology to monitor the human cytomegalovirus (HCMV)-specific CD8+ T-cell responses that is based on the detection of secreted interferon-gamma (IFN-gamma) in the whole blood (referred to as QuantiFERON -CMV). Evaluation of QuantiFERON -CMV in healthy individuals revealed that this technology was at least as sensitive and with some HCMV epitopes more sensitive than the ELISPOT for detecting ex vivo IFN-gamma. Results from QuantiFERON -CMV assays showed 97% (36/37 individuals) agreement with the anti-HCMV serology test in healthy individuals. Furthermore, we also show that this technology can be used to assess HCMV-specific T-cell responses in transplant patients. This study shows that QuantiFERON -CMV is a simple, reproducible, and reliable test for the detection of IFN-gamma in response to HCMV CD8+ T-cell epitopes, and may be a valuable diagnostic test for the detection of HCMV infection and a useful clinical tool for monitoring the immune response in immunosuppressed patients during therapy.

IL-1beta and IL-6 produced as part of the host response represent sensitive markers of sickness behaviour in humans with acute infection. Further work is needed to systematically characterize the spectrum and natural history of sickness behaviour in humans and to elucidate its biological basis.

Although the importance of CD4+ T cell responses to human cytomegalovirus (HCMV) has recently been recognized in transplant and immunosuppressed patients, the precise specificity and nature of this response has remained largely unresolved. In the present study we have isolated CD4 + CTL which recognize epitopes from HCMV glycoproteins gB and gH in association with two different HLA-DR antigens, DRA1*0101/DRB1*0701 (DR7) and DRA1*0101/DRB1*1101 (DR11). Comparison of amino acid sequences of HCMV isolates revealed that the gB and gH epitope sequences recognized by human CD4 + T cells were not only conserved in clinical isolates from HCMV but also in CMV isolates from higher primates (chimpanzee, rhesus and baboon). Interestingly, these epitope sequences from chimpanzee, rhesus and baboon CMV are efficiently recognized by human CD4 + CTL. More importantly, we show that gB-specific T cells from humans can also efficiently lyse peptide-sensitized Patr-DR7 + cells from chimpanzees. These findings suggest that conserved gB and gH epitopes should be considered while designing a prophylactic vaccine against HCMV. In addition, they also provide a functional basis for the conservation of MHC class II lineages between humans and Old World primates and open the possibility for the use of such primate models in vaccine development against HCMV.