Reducèd in vitro response to concanavalin A and lipopolysaccharide in senescent mice: a function of reduced number of responding cells

Abstract

The proliferative capacity of spleen cells from C57BL/6J female mice of various ages (3-28 months) to the polyclonal mitogens concanavalin A (Con A) and lipopolysaccharide (LPS) was examined. It was found that both the T and B cell population of the spleen demonstrate an age-related decrease in their capacity to respond in vitro. Peak responses to both mitogens occurs at about 1 year of age. This age-related reduction in response is expressed in the degree of incorporation of [3H]thymidine into DNA, the total number of cells generated in vitro, the number of labeled cells per culture and the number of blast cells per culture. The day of peak response in vitro does not change with age. Studies of the cell cycle of cells responding to Con A and to LPS from 12 and 28-month-old mice demonstrate that the generation time of individual proliferating cells does not alter with age. Nor does it differ for the B cells responding to LPS or the T cells responding to Con A. These studies also demonstrate that the proliferating cells from senescent mice are equally capable of repeated cell divisions as are the cells from the 1-year-old adult mouse. It is concluded that the defect in senescent mice which leads to a reduced in vitro response to the polyclonal mitogens LPS and Con A is a reduction in the number of responding cells and not an alteration in the capacity of those cells which do respond to divide.

T lymphocyte heterogeneity in old and young mice: functional defects in T cells selected for poor calcium signal generation

“…A decline, with age, in the proportion of T cells that can become activated has been previously inferred from analyses of cell cycle kinetics in alloantigen-and Con A-activated cells [16], from flow cytometric studies of cell cycle transitions using phytohemagglutinin-treated human peripheral blood cells [5- A poor response in Con A-stimulated LD cultures is characteristic not only of CaNR subsets isolated after Con A treatment, but also of CaNR cells obtained after exposure to anti-CD3 antibody or, most remarkably, ionomycin. These results are consistent with the hypothesis that T cells refractory to any one of these agents are refractory to all three.…”

Age-Related Changes in G₀-G₁ Transition and Proliferative Capacity of Mitogen-Stimulated Murine Spleen Cells

“…1973;Abraham et al, 1977], While with this method a marked decrease of these re sponses with age can be demonstrated, it does not allow any conclusion on the causes of such a decrease. In an attempt to further elucidate this question we have measured the early kinetics of the mitogen response of young and old spleen cells by comparing RNA synthesis as measured by cytofluorometry with synthesis of protein and DNA as measured by 3H-leucine and 3H-thymidine incorporation, respectively.…”

Aging and the Immune Response

“…Col lins, 1983;Miller, 1984;Sohnle et al, 1982), or numbers of high-affinity IL-2R (Schwab et al, submitted), each on a per responding cell basis, all suggest that there is little age-sensitive decline in those cells that can produce a detectable re sponse. The cytokinetic data are more equivocal: while some groups report a preservation of normal cell kinetic para meters in T cells that manage to enter G x (Abraham et al, 1977;Sohnle et al 1982;Staiano-Coico et al, 1984), most report age-associated deficits in cell cycle transi tion probabilities (Kubbies et al, 1985), average length of cycle (Tice et al, 1979), or numbers of cycles successfully negoti ated (Grossmann et al, 1989;Hefton et al, 1980;Negoro et al, 1986;Tice et al, 1979).…”