Adaptive Cellular Immunity To Human Cytomegalovirus

Primary HCMV infection induces robust CD8+ cytotoxic, and CD4+ helper, T-cell-mediated immune responses, which are associated with the resolution of acute primary infection: these responses are maintained at high frequency in long-term memory as the virus establishes persistent infection, with latency and periodic reactivation. Many of these T-cells are specific for epitopes in the pp65 and IE1 HCMV proteins, but it is apparent that many other viral proteins can also be T-cell targets, and in some individuals pp65 and IE1 responses are not immunodominant. During long-term carriage of the virus a balance is established between the T-cell-mediated immune response and viral reactivation: the T-cell response controls viral spread following reactivation, but the virus encodes multiple genes that interfere with MHC-I antigen processing (US 2, 3, 6 and 11), and with MHC-II processing and NK cell killing, allowing limited viral evasion of the response. Loss of this balance is most evident in the immunocompromised host in whom reactivation of latent virus or primary infection can lead to unchecked viral replication, with consequent disease and mortality. This chapter describes current understanding of CD8+ and CD4+ T-cell responses to HCMV, and how these responses reconstitute after bone marrow transplantation and might be used as therapies to protect against HCMV disease in immunocompromised subjects. The phenomenon of 'memory T-cell inflation' associated with HCMV and its relationship to immunosenescence is also discussed.