Immunodepression and Immunosuppression During Aging

Thomas‐Vaslin, Véronique; Six, Adrien; Pham, Hang-Phuong; Dansokho, Cira; Chaara, Wahiba; Gouritin, Bruno; Bellier, Bertrand; Klatzmann, David

doi:10.5772/29549

Cited by 7 publications

(25 citation statements)

References 104 publications

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“…FVB and B6 mice were chosen, because these strains belong to different phylogenetic clusters [45, 46] and display dissimilar T-Cell Receptor (TCR) repertoires as explained by chromosomal deletion of six Beta chain Variable region (BV) TCR families in FVB [47]. B6 and FVB mice differ in their lymphocyte and T cell compositions [48] and numbers in the various populations at steady-state [30]. Moreover, FVB mice display accelerated thymic involution and aging of VB repertoire as compared to B6 mice [30].…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, no clear consensus has been reached concerning the influence of genetics and age on T cell dynamics. We have previously observed that both the genetic background and aging affect T cell dynamics and repertoires [30]. Indeed, C57BL/6 and FVB mice differ in their T cell composition at steady state but also in their kinetics of T cell reconstitution after a transient immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, C57BL/6 and FVB mice differ in their T cell composition at steady state but also in their kinetics of T cell reconstitution after a transient immunosuppression. In FVB mice, there is an acceleration of thymic involution and of the immunological aging quantified by alterations in the homeostatic control of lymphocyte numbers and repertoire diversity in the periphery [30]. …”

Section: Introductionmentioning

confidence: 99%

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Modelling T cell proliferation: Dynamics heterogeneity depending on cell differentiation, age, and genetic background

Vibert

Thomas‐Vaslin

2017

PLoS Comput Biol

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Cell proliferation is the common characteristic of all biological systems. The immune system insures the maintenance of body integrity on the basis of a continuous production of diversified T lymphocytes in the thymus. This involves processes of proliferation, differentiation, selection, death and migration of lymphocytes to peripheral tissues, where proliferation also occurs upon antigen recognition. Quantification of cell proliferation dynamics requires specific experimental methods and mathematical modelling. Here, we assess the impact of genetics and aging on the immune system by investigating the dynamics of proliferation of T lymphocytes across their differentiation through thymus and spleen in mice. Our investigation is based on single-cell multicolour flow cytometry analysis revealing the active incorporation of a thymidine analogue during S phase after pulse-chase-pulse experiments in vivo, versus cell DNA content. A generic mathematical model of state transition simulates through Ordinary Differential Equations (ODEs) the evolution of single cell behaviour during various durations of labelling. It allows us to fit our data, to deduce proliferation rates and estimate cell cycle durations in sub-populations. Our model is simple and flexible and is validated with other durations of pulse/chase experiments. Our results reveal that T cell proliferation is highly heterogeneous but with a specific “signature” that depends upon genetic origins, is specific to cell differentiation stages in thymus and spleen and is altered with age. In conclusion, our model allows us to infer proliferation rates and cell cycle phase durations from complex experimental 5-ethynyl-2'-deoxyuridine (EdU) data, revealing T cell proliferation heterogeneity and specific signatures.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modelling T cell proliferation: Dynamics heterogeneity depending on cell differentiation, age, and genetic background

Vibert

Thomas‐Vaslin

2017

PLoS Comput Biol

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“…Immunization conditions and antigen doses are expected to lead to immune, tolerant, or hyper-reactivity conditions (12). Yet, in vivo perturbation and shrinking of the network through aging or transient depletion of dividing lymphocytes affect repertoire composition (16), tolerance (17), and memory maintenance leading to immunological amnesia (18). Therapies for regulation of inflammation by ‘T cell vaccination’ or homuncular self-antigen immunization, by inducing a regulatory anti-idiotypic network, are thus proposed to cure auto-immune diseases in the long run rather than global immunosuppression (19).…”

mentioning

confidence: 99%

“…Therapies for regulation of inflammation by ‘T cell vaccination’ or homuncular self-antigen immunization, by inducing a regulatory anti-idiotypic network, are thus proposed to cure auto-immune diseases in the long run rather than global immunosuppression (19). Otherwise, low-dose IL-2 administration to stimulate autoreactive Treg to control effector lymphocyte expansion during aging (16) or to prevent autoimmune diseases is promising.…”

mentioning

confidence: 99%

A Complex Immunological Idiotypic Network for Maintenance of Tolerance

Thomas‐Vaslin

2014

Front. Immunol.

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Individuation and the Organization in Complex Living Ecosystem: Recursive Integration and Self-assertion by Holon-Lymphocytes

Thomas‐Vaslin

2019

Acta Biotheor

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Individuation and organization in complex living multi-level ecosystem occurs as dynamical processes from early ontogeny. The notion of living "holon" displaying dynamic self-assertion and integration is used here to explain the ecosystems dynamic processes. The update of the living holon state according to the continuous change of the dynamic system allows for its viability. This is interpreted as adaptation, selection and organization by the human that observes the system at posteriori from its level. Our model concerns the complex dynamics of the adaptive immune system, integrating holon-lymphocytes that collectively preserve the identity and integrity of the organism. Each lymphocyte individualizes as a dynamic holon-lymphocyte, with somatic gene individuation leading to an individual, singular antigen immunoreceptor type, promoting the self-assertion. In turn, the "Immunoception" allows for perception of the environmental antigenic context, thus integration of the holon in its environment. The self-assertion/integration of holon-lymphocyte starts from fetal stages and is influenced by mother Lamarckian acquired historicity transmissions, a requisite for the integrity of the holobiont-organism. We propose a dynamic model of the perception by holon-lymphocyte, and at the supra-clonal level of the immune system functions that sustain the identity and integrity of the holon-holobiont organism.

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Immunodepression and Immunosuppression During Aging

Abstract: International audienc

Cited by 7 publications

References 104 publications

Modelling T cell proliferation: Dynamics heterogeneity depending on cell differentiation, age, and genetic background

Modelling T cell proliferation: Dynamics heterogeneity depending on cell differentiation, age, and genetic background

A Complex Immunological Idiotypic Network for Maintenance of Tolerance

Individuation and the Organization in Complex Living Ecosystem: Recursive Integration and Self-assertion by Holon-Lymphocytes

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