Splenic Niche Cells from Young Heterochronic Parabionts Have Decreased Capability to Amplify T-cell Proliferation in Vitro

Shytikov, Dmytro

doi:10.11648/j.ajbio.20150302.14

Cited by 5 publications

(5 citation statements)

References 38 publications

(48 reference statements)

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“…Also, during stimulation in vitro in the presence of autologous macrophages, T-cells from young heterochronic parabionts had a lower expression of NFκB p65 on early stages of stimulation (2 h) and a higher expression of IκBα on later stages (18 h) of stimulation when compared with T-cells from young isochronic parabionts. Observed data indicate the induction of negative changes in functions of macrophage-rich population of splenocytes during heterochronic parabiosis [33].…”

Section: Discussionmentioning

confidence: 90%

“…No considerable changes in the expression level of the IκBα protein in activated T-cells from different experimental groups were marked in this stage of activation. However, the level of the activated form of caspase 3 (p20) was still considerably higher in T-cells from young isochronic and young heterochronic parabionts in comparison with T-cells from either old isochronic or heterochronic parabiotic animals [33].…”

Section: The Study Of Age-related Changes Of Lymphoid Niche Cells In mentioning

confidence: 89%

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The Rejuvenation of the Immune System: Physiological, Cellular, and Molecular Mechanisms

Pishel¹,

Butenko²

2016

Molecular Mechanisms of the Aging Process and Rejuvenation

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Abstract"ge-related immune dysfunction has been confirmed by many studies. "ll of these changes result in increased susceptibility to infectious diseases and pathological conditions associated with inflammation or autoreactivity. To prevent these changes, we used various model approaches as follows i the models of hematopoietic stem cells HSCs transplantation in irradiated chimeras, ii the model of heterochronic parabiosis that provides regular physiological exchange by blood factors between partners, and iii cocultivation of lymphoid cells and niche-forming cells in vitro to determine its intercellular communication mechanisms. It was shown that the old HSCs equally effectively restore the immune system of young animals and their own. "ut, the young hematopoietic cells behaved like old in the old organism. Parabiosis model demonstrated that regular exchange by blood factors between heterochronic partners does not lead to the old system rejuvenation. "nd we observed impaired capacity of splenic CD c + DC and macrophages from young heterochronic parabionts to co-stimulate proliferation of T-cells in vitro with statistically significant decrease in nuclear factorkappa " NFκ" p and increased expression of Iκ"α during early activation events. These findings suggest that age-related changes in the immune system are multifactor process, and whole-system environment of the organism plays a crucial role in the occurrence of age-related immune system alterations.

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Section: Discussionmentioning

confidence: 90%

Section: The Study Of Age-related Changes Of Lymphoid Niche Cells In mentioning

confidence: 89%

The Rejuvenation of the Immune System: Physiological, Cellular, and Molecular Mechanisms

Pishel¹,

Butenko²

2016

Molecular Mechanisms of the Aging Process and Rejuvenation

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“…in the case of impaired Schwann cell function [17], impaired T cell subset distribution [18], function [19] and thymic involution [18,20], and in the first two examples pro-geronic effects were noted in the adult animal. Regarding individual pro-geronic molecules, increased levels of CCL11 and b2m with age are associated with decreased brain functions [8,11] and increased b-catenin signalling was implicated in defects in bone repair [14].…”

Section: Heterochronic Parabiosis As Means To Study Ageing and (Immunmentioning

confidence: 99%

“…With regard to ageing of the immune system, Pishel et al published observations of accelerated ageing of the immune system as determined by the failure to restore thymic mass of the old animal and an increase of CD44 1 memory T cells in the young animal and diminished T cell proliferation and T cell receptor (TCR) signalling upon invitro stimulation [18,19]. These studies did not use congenic markers to distinguish between adult and old T cells in critical experiments, and conducted bulk T cell assays that do not account for the different proportions of T cell subsets with age.…”

Section: Heterochronic Parabiosis As Means To Study Ageing and (Immunmentioning

confidence: 99%

Homeostatic migration and distribution of innate immune cells in primary and secondary lymphoid organs with ageing

Nikolich‐Žugich

Davies

2017

Clinical and Experimental Immunology

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SummaryAgeing of the innate and adaptive immune system, collectively termed immune senescence, is a complex process. One method to understand the components of ageing involves dissociating the effects of ageing on the cells of the immune system, on the microenvironment in lymphoid organs and tissues where immune cells reside and on the circulating factors that interact with both immune cells and their microenvironment. Heterochronic parabiosis, a surgical union of two organisms of disparate ages, is ideal for this type of study, as it has the power to dissociate the age of the cell and the age of the microenvironment into which the cell resides or is migrating. So far, however, it has been used sparingly to study immune ageing. Here we review the limited literature on homeostatic innate immune cell trafficking in ageing in the absence of chronic inflammation. We also review our own recent data on trafficking of innate immune subsets between primary and secondary lymphoid organs in heterochronic parabiosis. We found no systemic bias in retention or acceptance of neutrophils, macrophages, dendritic cells or natural killer cells with ageing in primary and secondary lymphoid organs. We conclude that these four innate immune cell types migrate to and populate lymphoid organs (peripheral lymph nodes, spleen and bone marrow), regardless of their own age and of the age of lymphoid organs.

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“…These changes were expressed by a decrease in the CD4/CD8 ratio, and an increase in the number of CD8+44+ and CD4+44+ memory cells in the spleen. The study of the mechanism of such rapid age-related changes in the immune system of young heterochronous partners showed that it may be associated with thymus atrophy [83], or disturbance in exposure to "aged" antigenpresenting cells of the microenvironment of lymphoid organs [84][85][86], or a paradoxical decrease in regulatory FoxP3+CD4+25+ T cells in old partners [83]. It is known that a decrease in the number of Tregs can lead to homeostatic T cell proliferation [87,88].…”

Section: Systemic Blood and Cells Exchange In Heterochronic Parabiosismentioning

confidence: 99%

Immune system rejuvenation—approaches and real achievements

Pishel

2023

Explor Immunol

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Interest in the mechanisms of aging of the immune system has not faded over the past 100 years, and it is caused by the immune-mediated development of age-related pathology, including autoimmune organ damage, reduced vaccination efficiency, atherosclerosis, the development of cardiovascular pathology, etc. In contrast to many other organs and systems, the immune system aging begins at an early age and has more pronounced changes that lead to the development of secondary pathology, which significantly affects life expectancy. But an effective strategy to restore immune function has not been developed yet. During this time, the mechanisms of age-related dysfunction of organs and cells of both the adaptive and innate immune systems were studied in detail—thymus involution, a decrease in the potential of hematopoietic stem cells, impaired differentiation and functions of immunocompetent cells, as well as the ways of their interaction. Numerous potential therapeutic targets have been identified and various approaches have been used to implement such therapeutic interventions. The review is devoted to replacement therapy using transplantation of hematopoietic stem cells (HSCs) and young lymphoid cells and tissues, cellular and systemic factor exchange in heterochronic parabiosis, and some other widely used life extension approaches. It has been proven that cell therapy using young cells to rejuvenate the old immune system, unfortunately, often turns out to be ineffective because it does not eliminate the root cause of age-related changes. The phenomenon of inflamm-aging that develops with age can significantly affect both the aging of the organism in general and the functioning of immunocompetent cells in particular. Therefore, the most promising direction in the restoration of immune functions during aging is systemic approaches that have a complex effect on the organism as a whole and can slow down the aging process.

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Splenic Niche Cells from Young Heterochronic Parabionts Have Decreased Capability to Amplify T-cell Proliferation in Vitro

Cited by 5 publications

References 38 publications

The Rejuvenation of the Immune System: Physiological, Cellular, and Molecular Mechanisms

The Rejuvenation of the Immune System: Physiological, Cellular, and Molecular Mechanisms

Homeostatic migration and distribution of innate immune cells in primary and secondary lymphoid organs with ageing

Immune system rejuvenation—approaches and real achievements

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