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      Slower immune system aging in women versus men in the Japanese population

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          Abstract

          Background

          Gender-related differences in humans are commonly observed in behaviour, physical activity, disease, and lifespan. However, the notion that age-related changes in the immune system differ between men and women remains controversial. To elucidate the relationship between immunological changes and lifespan, peripheral blood mononuclear cells from healthy Japanese subjects (age range: 20–90 years; N = 356) were analysed by using three-colour flow cytometry. The proliferative activities and cytokine-producing capacities of T cells in response to anti-CD3 monoclonal antibody stimulation were also assessed.

          Results

          An age-related decline in the number of T cells, certain subpopulations of T cells (including CD8 + T cells, CD4 +CDRA + T cells, and CD8 +CD28 + T cells), and B cells, and in the proliferative capacity of T cells was noted. The rate of decline in these immunological parameters, except for the number of CD8 + T cells, was greater in men than in women (p < 0.05). We observed an age-related increase or increasing trend in the number of CD4 + T cells, CD4 +CDRO + T cells, and natural killer (CD56 +CD16 +) cells, as well as in the CD4 + T cell/CD8 + T cell ratio. The rate of increase of these immunological parameters was greater in women than in men (p < 0.05). T cell proliferation index (TCPI) was calculated from the T cell proliferative activity and the number of T cells; it showed an age-related decline that was greater in men than in women (p < 0.05). T cell immune score, which was calculated using 5 T cell parameters, also showed an age-related decline that was greater in men than in women (p < 0.05). Moreover, a trend of age-related decreases was observed in IFNγ, IL-2, IL-6, and IL-10 production, when lymphocytes were cultured with anti-CD3 monoclonal antibody stimulation. The rate of decline in IL-6 and IL-10 production was greater in men than in women (p < 0.05).

          Conclusion

          Age-related changes in various immunological parameters differ between men and women. Our findings indicate that the slower rate of decline in these immunological parameters in women than that in men is consistent with the fact that women live longer than do men.

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          Most cited references27

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          Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans.

          Components of the innate immune response, including neutrophils and macrophages, are the first line of defense against infections. Their role is to initiate an inflammatory response, phagocyte and kill pathogens, recruit natural killer cells (NK), and facilitate the maturation and migration of dendritic cells that will initiate the adaptive immune response. Extraordinary advances have been made in the last decade on the knowledge of the receptors and mechanisms used by cells of the innate immunity not only to sense and eliminate the pathogen but also to communicate each other and collaborate with cells of adaptive immunity to mount an effective immune response. The analysis of innate immunity in elderly humans has evidenced that aging has a profound impact on the phenotype and functions of these cells. Thus altered expression and/or function of innate immunity receptors and signal transduction leading to defective activation and decreased chemotaxis, phagocytosis and intracellular killing of pathogens have been described. The phenotype and function of NK cells from elderly individuals show significant changes that are compatible with remodeling of the different NK subsets, with a decrease in the CD56bright subpopulation and accumulation of the CD56dim cells, in particular those differentiated NK cells that co-express CD57, as well as a decreased expression of activating natural cytotoxicity receptors. These alterations can be responsible of the decreased production of cytokines and the lower per-cell cytotoxicity observed in the elderly. Considering the relevance of these cells in the initiation of the immune response, the possibility to reactivate the function of innate immune cells should be considered in order to improve the response to pathogens and to vaccination in the elderly. Copyright © 2012 Elsevier Ltd. All rights reserved.
            • Record: found
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            Age-related changes in lymphocyte development and function.

            The effects of aging on the immune system are widespread and extend from hematopoietic stem cells and lymphoid progenitors in the bone marrow and thymus to mature lymphocytes in secondary lymphoid organs. These changes combine to result in a diminution of immune responsiveness in the elderly. This review aims to provide an overview of age-related changes in lymphocyte development and function and discusses current controversies in the field of aging research.
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              • Abstract: found
              • Article: not found

              Changes in CD8 and CD4 lymphocyte subsets, T cell proliferation responses and non-survival in the very old: the Swedish longitudinal OCTO-immune study.

              Results from a previous longitudinal study indicated that a combination of high CD8 and low CD4 percentages and poor T cell proliferation in peripheral blood lymphocytes was associated with higher mortality in a subgroup of a sample of very old Swedish individuals. The present study examined whether those results could be confirmed at a subsequent 2-year time interval by investigating if additional individuals from the same original sample had developed the immune profile associated with higher mortality. Subgroups were formed by cluster analysis and similar to our previous results, this follow-up study identified a subgroup of subjects (n = 18) with an immune profile which again included high CD8, low CD4 percentages and poor mitogen response and was associated with higher mortality. Over the 2-year period 12 additional individuals: (1) Developed this immune profile; and (2) Could be identified by changes in their CD4:CD8 ratios which progressively decreased over the study period. These results confirm our original study and indicate that in this very old sample, over a subsequent 2 year period, additional individuals moved into the cluster at risk for higher mortality.

                Author and article information

                Journal
                Immun Ageing
                Immun Ageing
                Immunity & Ageing : I & A
                BioMed Central
                1742-4933
                2013
                15 May 2013
                : 10
                : 19
                Affiliations
                [1 ]Institute for Health and Life Sciences, Tokyo Medical & Dental University Open Laboratory, Medical Research Institute Surugadai Bldg, 2-3-10, Surugadai, Kanda, Chiyoda-ku, Tokyo 101-0062, Japan
                [2 ]Department of Comprehensive Pathology, Tokyo Medical & Dental University, Tokto, Japan
                [3 ]Nakanosogo Hospital, Tokto, Japan
                [4 ]UCLA, Los Angeles, USA
                [5 ]Research Center on Aging, University of Sherbrooke, Sherbrooke, Canada
                Article
                1742-4933-10-19
                10.1186/1742-4933-10-19
                3663722
                23675689
                39d3455a-eccf-43f1-9def-fe28e5fa4610
                Copyright ©2013 Hirokawa et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 November 2012
                : 19 April 2013
                Categories
                Research

                Immunology
                ageing,immune system,gender difference,t cells,t cell immune score,t cell proliferation index,cd8+cd28+ t cells

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