Age-related changes in immune reactivity: the influence of intrinsic defects and of a changed composition of the CD4+ T cell compartment.

Aging is accompanied by a decline in immune reactivity which to a major extent can be attributed to changes at the level of regulatory CD4+ T cells. In addition to evidence pointing to intrinsic defects, resulting in improper responsiveness of lymphocytes, it is likely that many age-related phenomena can be explained by a changed composition of the T cell compartment. Most likely as a consequence of thymic involution, the fraction of naive T cells in the periphery decreases, resulting in poor responses to neoantigens in particular. Moreover, due to antigenic exposure the fraction of memory cells increases. It is likely that, regardless of their phenotype, cells from aged individuals are subject to intrinsic defects or to immunosuppression, resulting in a lower responsiveness. As far as CD4+ T cells are concerned, recent studies have demonstrated that naive and memory cells behave differently with regard to activation requirements and lymphokine production. Age-related changes in T cell reactivity will be discussed in the context of these observations.