Significant presence of terminally differentiated T cells and altered NF-kappaB and I-kappaBalpha interactions in healthy ageing.

The risk of infection and cancer increases dramatically beyond middle age, when T-cell function is noticeably altered. Nevertheless, many elderly people remain in apparently good health. To identify immunological adaptations favouring longevity, a pilot study was undertaken to compare peripheral blood T cells from healthy volunteers aged 18-25 years with those >65 years. Instead of preserved immune function in the elderly, there was an emergence of haematopoietic space particularly affecting T- and B-cell numbers, together with early signs of immunoglobulin dysregulation. Age-associated proliferative defects were present irrespective of the stimuli used. A higher constitutive expression of NF-kappaB and I-kappaBalpha in the nuclei of peripheral lymphocytes from the elderly remained unaltered by activation stimuli, despite the presence of exogenous cytokines. Nevertheless, activation resulted in their higher CD95 upregulation and more intracellular bcl-2 (suggesting a survival advantage), but lower CD27, CD28 and CD45Rb expression. The presence of CD45RO(+) CD45Rb(-) populations was unique to the elderly and their lower replicative potential was not due to the presence of CD25(+) regulatory T cells. These data collectively suggest altered gene regulation and the accumulation of terminally differentiated T cells during healthy ageing.