Effect of age on functional plasticity of CD4+ T cells infiltrating a localized secondary immune response in humans

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Aging is accompanied by a marked susceptibility to infectious diseases, which inflict heavy toll upon the rapidly aging society with regard to lost productivity, mounting health costs and loss of life. The progressive decline with age of the immune system - immunosenescence - is the primary underlying cause of the age-related increase in this susceptibility. Despite decades of research, important gaps remain in our understanding of the fundamental nature of the process, as well as in our practical ability to protect older adults against infectious diseases. Our bodies mount immune responses when attacked by infectious organisms. The central participants in this response are our white cells (leucocytes), whose role is to protect us from the infective agents. Based on the molecules they secrete different populations (subsets) of leucocytes have been identified which play different roles during immune responses. A separate subset of leucocytes is known as regulatory cells and their main role is the control of other leucocytes. The major problems that are inherent in the study of human immunology is that generally, only leucocytes from the blood compartment are studied and that virtually all studies are performed in vitro. We have developed and validated a new model for the study of a human memory T cell response in humans in vivo. This involves the injection of a recall antigen in the skin, followed by either the biopsy of the lesion for histological analysis of the immune infiltration, or the harvest of infiltrating cells using suction blister technology. Using this model, we propose to clarify the functional profile of cells that accumulate in the skin during immune responses induced by different antigens and determine whether these leucocyte populations behave differently in the old individuals. Specifically we wish to examine the relationship between regulatory cells and other functional leucocyte populations and explore mechanisms which control their behaviour. This information may enable us to manipulate this balance artificially.