The role of CD8+ T-cell subpopulations in old age

Aging is frequently associated with the development of a chronic pro-inflammatory status. This hampers the production of antibodies, endangers the protective effect of vaccinations and is also well documented to exacerbate the development and progression of age-related diseases such as Alzheimer`s Disease and atherosclerosis. Little information is presently available on possible causes of chronic inflammation in old age. Only recently, it has become known that the excessuve production of the cytokine Interferon- by a certain CD8 + T-lymphocyte subset that characteristically accumulates in elderly persons may play an important role. The possible detrimental effects of this T-cell subset may in some elderly persons, however, be counterbalanced by the accumulation of another CD8 + T-cell subpopulation which characteristically produces Interleukin-4 but not Interferon- . This latter T-cell subset, which is likely to occur in healthy elderly persons still capable of producing antibodies following immunisations, has only recently been first described by the applicant`s group. The present proposal aims at investigating the origin and function of these partly antagonistic T-cell subpopulations, which accumulate in the aging immune system. It is the goal of the project to verify our hypothesis that depending on lifelong environmental influences differentiation and accumulation of different T-lymphocytes subtypes take place. The balance between these subsets may well be decisive, whether immune function is maintained or immune dysfunction develops in the elderly.

It was the goal of this project to gain a better understanding of age-related changes within the immune system in order to find new ways to prevent loss of immune function with age. Age-related changes in T lymphocytes, immune cells responsible for eliminating virus-infected cells and cancer cells from the body, are most detrimental. This is due to early degenerative changes that take place in the thymus, the organ in which T cells mature. As the thymus gradually loses its ability to replenish, the populations of nave T cells, memory and effector T cells increase in number and dominate the repertoire. This can lead to the loss of certain T cell specificities and changes in the polarization of the immune system. In the course of the project we succeeded in characterizing two CD8 + T cell types which specifically occur in elderly persons: CD28 - effector cells, the accumulation of which is frequently associated with cytomegalovirus (CMV) and correlates with a humoral non-responder status to vaccination, and CD25-expressing, non-regulatory CD8 + memory T cells which seem to be associated with a good humoral immune response in old age. CD8 + CD28 - cells produce large amounts of proinflammatory cytokines, have a very restricted repertoire and short telomeres. Their accumulation therefore causes inflammatory processes which are a prerequisite for the aggravation and perpetuation of age-related diseases such as Alzheimer`s disease or atherosclerosis. In contrast, CD8 + CD25 + memory cells produce IL-2 and IL-4, have a diverse repertoire and the potential to recognize a high number of different antigens. Due to their relatively long telomeres, these cells also have a good proliferative potential. In the absence of functioning nave T cells CD8 + CD25 + cells seem to be a valuable line of defense to protect elderly persons from disease.