The involvement of the intestinal microflora in the expansion of CD4+ T cells with a naive phenotype in the periphery.

It is well known that immune reactivity declines with age. Recently, we demonstrated that the age-related decrease in IL-2 production by CD4+ T cells was accompanied by an increased production of IL-4 and interferon-gamma (IFN-gamma). This age-related shift in the profile of lymphokine production was related to phenotypic changes within the CD4+ T-cell subset, that is, a decrease in the percentage of CD45RB++ CD4+ T cells and an increase in the percentage of Pgp-1+ CD4+ T cells.

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.

Age-related changes in lymphokine production related to a decreased number of CD45RBhi CD4+ T cells.

The ability of CD4+ T cells from CBA/Rij mice to produce interleukin (IL) 2 after stimulation with anti-CD3, concanavalin A, or the combination of phorbol 12-myristate 13-acetate and ionomycin declines during aging. This phenomenon was accompanied by an increased production of IL 4 and interferon-gamma. These age-related changes in lymphokine production correlated with the decrease in the percentage of CD45RBhi CD4+ T cells from about 80% in 2-month-old to about 40% in 27-month-old mice.

Impairment of CD3-dependent and CD3-independent activation pathways in CD4+ and in CD8+ T cells from old CBA/RIJ mice.

Stimulation of T cells from old mice with anti-CD3 antibodies resulted in a high variability of proliferative responses, which were 2- to 8-fold lower than the responses by T cells from young mice, even in the presence of exogenous rIL-2. Moreover, the CD4+ T cells from these old mice displayed a diminished capacity to produce IL-2 in response to anti-CD3. A partial explanation was found in the observation that T cells from the majority of old mice displayed a diminished expression of CD3 of variable intensity.

A decreased functional capacity of CD4+ T cells underlies the impaired DTH reactivity in old mice.

The data presented in this paper show that the in vivo delayed-type-hypersensitivity (DTH) reaction to both H-2 and non-H-2 alloantigens declines with increasing age. It is also shown that cells generated in vitro are capable to transfer DTH to young naive syngeneic recipients. Using this in vitro system it could be demonstrated that cells from old CBA/Rij mice induced lower DTH responses than cells from young CBA/Rij mice.