Decreased sensitivity to dexamethasone in lymphocytes from patients with Alzheimer's disease.

Cortisol levels in patients with Alzheimer's disease (AD) are relatively unaffected by a challenge with dexamethasone (DEX) in vivo. The present study demonstrates that DEX is less inhibitory for phytohemagglutinin (PHA)-induced T cell proliferation in AD patients as compared to age-matched controls. Since no significant differences were found between AD patients and age-matched controls with regard to the fraction of CD45RA+ or CD45RO+ CD4+ T cells nor the ability of peripheral blood mononuclear cells to produce IL-2 or IL-4, it is unlikely that the difference in DEX sensitivity is due to a changed lymphokine profile or a changed composition of the CD4+ T cell population.

Mel14+ CD4+ T cells from aged mice display functional and phenotypic characteristics of memory cells.

Aging is accompanied by an increased fraction of memory CD4+ T cells. Despite the fact that human memory cells have been reported to produce high levels of IL-2, studies in mice and man indicate an age-related decline in IL-2 production. In the present study, we examined whether these conflicting results depend on the activation pathway employed in a comparison of phenotypically distinct CD4+ T cells from young and aged mice.

The sensitivity of IL-4 production for cAMP inducers is lost in CD4+ T cells from aged mice.

CD4+ T cell clones have been demonstrated to display a differential sensitivity for the induction of cAMP. In the present study we investigated whether the differential sensitivity of CD4+ T cell clones for cAMP inducers is also applicable to freshly isolated phenotypically and functionally distinct CD4+ T cell subsets that develop naturally in aging mice. Our results show that the concanavalin A induced and anti-CD3 induced proliferative response of CD4+ T cells from young mice is more sensitive for prostaglandin E2 (PGE2) and forskolin than that of their aged counterparts, although the IL-2 production by these cells was equally sensitive.

The acquisition of a memory phenotype by murine CD4+ T cells is accompanied by a loss in their capacity to increase intracellular calcium.

During the process of aging, the fraction of CD4+ T cells with a naive phenotype, that is, Pgp-1- CD45RBHighMEL-14+, decreases in favor of CD4+ T memory cells. Total CD4+ T cells from aged mice displayed a diminished calcium response to anti-CD3 and even ionomycin as compared to the cells from young mice, and this was related to the changed composition of the CD4+ T-cell population. Regardless the age of the donor mice, naive CD4+ T cells effectively increased intracellular calcium, whereas memory CD4+ T cells were impaired in this regard.