SUMMARYWe have previously shown that physiological hormone differences related to pregnancy or sex affect the age-related distribution of mononuclear cell populations during murine ageing. To determine whether such changes are involved in the age-related changes in functions of T cells, we examined the secretion of major T cell immunoregulatory cytokines (IL-2, IL-4, interferon-gamma (IFN-g), IL-3, IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF)) of in vitro concanavalin A-activated spleen cells of C57Bl/6 mice. The study included multiparous and virgin females and males at 2, 8, 15 and 23 months of age. Short-term effects of parity (8 months) were evidenced by the decrease of IFN-g and the preserved IL-2 production in multiparous females (8 months), while IFN-g was unchanged and IL-2 decreased in virgin mice. The increase in IL-4 production appeared earlier in multiparous females (15 months) than in virgin mice (23 months). The increase in IL-4/IFN-g and IL-4/IL-2 ratios at 8 and 15 months, respectively, in multiparous females, suggests that pregnancy modifies the Th1/Th2 equilibrium. In late adulthood (15 months), IL-6 and GM-CSF production was higher in multiparous females than in virgin males or females. Sex differences were also noticed: IFN-g secretion capacity was lower in males than in females during ageing. This study underlines that the onset, magnitude and kinetics of the age-related changes in cytokine production are parity-and sex-dependent. These changes probably influence the incidence of age-related diseases and may explain the greater longevity of females.
SUMMARYSo far all studies on the murine ageing process have been conducted on virgin mice. Immune ageing may be influenced by sex hormone differences related to sex or pregnancies. The aim of this study was to investigate whether pregnancies and gender influence the cell changes observed during ageing in a peripheral lymphoid compartment of C57Bl/6 mice. Using flow cytometry, changes in (Thy1:2 þ ) T cell, (B220 þ ) B cell and (CD11b/Mac-1) macrophage spleen populations were monitored in 2, 8 (3 months after last pregnancy) 15 and 23-month-old mice including males, virgin and multiparous females. The development of naive (CD44 low ), memory (CD44 high ), activated/memory (MEL-14, CD62L) cells were investigated in CD4 þ and CD8 þ T cell subsets. Both short term (at 8 months) and long term (at 15 and 23 months) effects of multiparity were obvious in the lymphocyte/macrophage population changes associated with the ageing process. Short-term effects included delayed appearance of CD4 þ CD44 high memory lymphocytes and increased numbers of both CD4 þ MEL-14 low activated/memory cells and Mac-1 þ macrophages when compared with virgin control mice. Later effects of multiparity were increased CD8a dull populations and increased T/B cell ratios and the ratio of memory to naive CD4. A sex effect was noticed: males exhibited lower Mac-1 þ levels and memory/naive ratio in CD4 þ subset than virgin females throughout life. These results suggest that gender and/or pregnancies affect the age-related distribution of lymphoid and macrophage cell populations in the spleen of C57Bl/6 mice.
SUMMARYWe recently reported that pregnancy affects age-related changes in the distribution of lymphoid and macrophage populations in the spleen of C57Bl/6 mice. In the present study, we examined the in¯uence of pregnancies on the generation of various developmental B-cell subsets and granulocyte/macrophage lineage cells during murine ageing. Using¯ow cytometry, changes in lymphoid (mature and early B-cell precursors: B220 high , B220 low , surface immunoglobulin M (sIgM) m chain +/±) and myeloid (monocyte/macrophage Mac-1/CD11b, granulocyte Gr-1/Ly-6G) compartments were monitored in the bone marrow of young (2 months) and 15-and 23-month-old mice including male, multiparous and virgin female mice. Pregnancies delayed the age-related decline in murine B lymphopoiesis and maintained B-cell reserve capacity during ageing. We also found an increased production of myeloid cells induced by pregnancies at middle (15 months) and advanced (23 months) ages. This comparative study provides new information on changes in marrow lymphopoiesis and myelopoiesis with age. Our data emphasizes that the onset, magnitude and kinetics of age-related changes in the haematopoietic marrow are parity dependent. These changes could in¯uence the incidence of age-related diseases and may account for the greater longevity of females.
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