What are the consequences for the immune system of persistent antigen stimulation by cytomegalovirus? (360G-Wellcome-081986_B_07_Z)

CMV has a major impact on the human immune system, generating very high frequencies of antigen specific CD4 and CD8 T cells. CMV-seropositivity is also a component of the immune risk phenotype and is predictive of poor survival in elderly individuals. In this proposal we will determine whether CMV-specific immune responses differ from those to antigens that are only intermittently present, in T cell kinetics, in the type of effector cells generated and in the rate of turnover of responding T cell clones. We will also determine how great is the extent of contraction of the T cell repertoire in elderly CMV-seropositive and seronegative donors. Finally we shall determine whether the titre and avidityof anti-CMV antibody alter in the elderly and whether a large fraction of memory B cells are directed toward CMV antigens, as is the case for T cells. These data will throw light on the mechanisms by which CMV alters immune function in the elderly.