Lacy, K.E.; (2008) The effects of ageing on cutaneous immunity. Doctoral thesis , University of London.

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Abstract

This work investigated the effects of ageing on the cutaneous response to the injection of bacterial, fungal and viral antigens in humans. Previous studies have shown reduced cutaneous delayed type hypersensitivity (DTH) responses in the old and it has been assumed that this is due to an overall decline in cell-mediated immunity that occurs with ageing. However, it has remained unclear as to whether DTH responses in old skin are truly reflective of immune responses in all compartments of the immune system. Reduced clinical responsiveness in the skin to the intradermal injection of antigen was identified despite good peripheral T cell responses in the old and it was hypothesised that this may be reflective of a skin-specific defect that occurs during ageing. Possible mechanisms for this were investigated by performing both skin suction blisters and skin biopsies following injection of antigen into the skin. In the old there was a significant reduction in the infiltration of CD4+ lymphocytes in the skin that correlated with a reduced clinical response. A reduction in CXCR3 expression was found on CLA+CD4+ T cells isolated from the peripheral blood in old subjects. In addition, a reduction in the levels of cutaneous pro-inflammatory mediators was identified. This was associated with reduced CD4+ T cell activation and proliferation in situ as determined by CD69 and Ki67 expression on lymphocytes isolated directly ex vivo from the skin. A defect in initiation of the DTH response was considered. Although a possible decrease in the numbers of CD14+ monocytes was identified, no difference in monocyte activation or the numbers of CD1a or DC-SIGN positive dendritic cells was found in the old. The data suggests that both decreased cell migration in to the skin in addition to decreased expansion of infiltrating cells contributes to the defective cutaneous response to antigenic challenge during ageing.

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