Bidirectional Effects of Corticosterone on Splenic T-Cell Activation: Critical Role of Cell Density and Culture Time

Wiegers, G. Jan; Stec, IE; Klinkert, W.; Linthorst, Astrid C E; Reul, Johannes M. H. M.

doi:10.1159/000054630

Cited by 13 publications

(6 citation statements)

References 25 publications

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“…The authors also found a moderate inhibition of CD4 expression after 96-120 h which is consistent with our observations [19]. However, in further experiments they showed that the enhancing effect on proliferation during the first 48-72 h of culture was due to culture conditions [20]. At low densities T-cell proliferation was inhibited by corticosterone irrespective of the culture time [20].…”

Section: Discussionsupporting

confidence: 88%

“…However, in further experiments they showed that the enhancing effect on proliferation during the first 48-72 h of culture was due to culture conditions [20]. At low densities T-cell proliferation was inhibited by corticosterone irrespective of the culture time [20]. Down-regulation of CD4 by dexamethasone (10 −8 to 10 −6 M) has also been described in TNF-␣-stimulated eosinophils [21].…”

Section: Discussionmentioning

confidence: 97%

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Rimexolone inhibits proliferation, cytokine expression and signal transduction of human CD4+ T-cells

et al. 2010

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 97%

Rimexolone inhibits proliferation, cytokine expression and signal transduction of human CD4+ T-cells

et al. 2010

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“…There are numerous in vivo and in vitro reports on corticosteroids and their analogues which effect thymocyte apoptotsis and which also have adverse effects on peripheral T cell activation events. [76][77][78][79][80][81][82] However, a previous study by Wienberg et al 34 demonstrated that TREC levels increased in cord blood transplant recipients even while receiving low-dose steroids as GVHD prophylaxis. However, this data does not exclude the possibility that high dose corticosteroids used in GVHD treatment would have an adverse effect on thymic output.…”

Section: Discussionmentioning

confidence: 96%

Factors affecting reconstitution of the T cell compartment in allogeneic haematopoietic cell transplant recipients

Fallen

McGreavey

Madrigal

et al. 2003

Bone Marrow Transplant

105

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Summary:The factors affecting T cell reconstitution post haematopoietic cell transplantation (HCT) are not well characterised. We carried out a longitudinal analysis of T cell reconstitution in 32 HCT recipients during the first 12 months post transplant. We analysed reconstitution of naı¨ve, memory and effector T cells, their diversity and monitored thymic output using TCR rearrangement excision circles (TRECs). Thymic-independent pathways were responsible for the rapid reconstitution of memory and effector T cells less than 6 months post HCT. Thymic-dependent pathways were activated between 6 and 12 months in the majority of patients with naı¨ve T cell numbers increasing in parallel with TREC levels. Increasing patient age, chronic GVHD and T cell depletion (with or without pretransplant Campath-1H) predicted low TREC levels and slow naı¨ve T cell recovery. Furthermore, increasing patient age also predicted high memory and effector T cell numbers. The effects of post HCT immunosuppression, total body irradiation, donor leucocyte infusions, T cell dose and post HCT infections on T cell recovery were also analysed. However, no effects of these single variables across a variety of different age, GVHD and T cell depletion groups were apparent. This study suggests that future analysis of the factors affecting T cell reconstitution and studies aimed at reactivating the thymus through therapeutic intervention should be analysed in age-, GVHD-and TCD-matched patient groups. While each of these parameters may have mutually exclusive effects on the outcome of the transplant, it is the combination of all of these parameters that will determine the ultimate success of the transplant. Furthermore, the effects of each of these parameters on immune reconstitution post HCT are unclear.The immediate post transplant period is followed by a severe and often prolonged immune deficiency that results in prolonged susceptibility to infection. 8,17,[19][20][21][22] Although infections that occur in the first month after engraftment probably result from deficiencies in both granulocytes and other mononuclear cell subsets, the more prolonged immune deficiency arises from deficiencies in effective CD4 þ T cell and B cell reconstitution and immunosuppressive therapy. 23,[27][28][29] It was then suggested that the reconstitution and maintenance of effective T cell immunity after HCT was dependent on education of T cell precursors in the thymus. [30][31][32] Furthermore, these observations generated considerable interest in the factors affecting the reconstitution of T cell immunity through thymic-dependent pathways. 33,34 Using phenotypic markers of T cell naivety (primarily the CD45RA antigen), initial studies demonstrated that increasing patient age had an adverse effect on the regeneration of naı¨ve CD4 þ T cells, presumably due to age-related thymic involution, 31 observations that were confirmed using the TCR rearrangement excision circle (TREC) assay to measure thymic output. 35,36 In addition, the thymus has been demonstrated to be...

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“…Other studies have suggested that low concentration corticosterone-induced enhancement of concanavalin A-stimulated mitogenesis of splenocytes from ADX animals may be mediated by the type-1 or mineralocorticoid receptor [77] . Finally, it was shown that corticosterone increases T-cell responsiveness to IL-2 and proliferation under conditions of high cell densities in vitro, that mimic conditions that are likely to be found in lymph nodes in vivo [78] . Thus, these in vitro studies indicate a possible mechanism by which stress and stress hormones may enhance immune function in vivo.…”

Section: Bidirectional Effects Of Glucocorticoid Hormones On Immune Fmentioning

confidence: 88%

Enhancing versus Suppressive Effects of Stress on Immune Function: Implications for Immunoprotection and Immunopathology

Dhabhar¹

2009

Neuroimmunomodulation

691

577

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Stress is known to suppress immune function and increase susceptibility to infections and cancer. Paradoxically, stress is also known to exacerbate asthma, and allergic, autoimmune and inflammatory diseases, although such diseases should be ameliorated by immunosuppression. Moreover, the short-term fight-or-flight stress response is one of nature’s fundamental defense mechanisms that enables the cardiovascular and musculoskeletal systems to promote survival, and it is unlikely that this response would suppress immune function at a time when it is most required for survival (e.g. in response to wounding and infection by a predator or aggressor). These observations suggest that stress may suppress immune function under some conditions while enhancing it under others. The effects of stress are likely to be beneficial or harmful depending on the type (immunoprotective, immunoregulatory/inhibitory, or immunopathological) of immune response that is affected. Studies have shown that several critical factors influence the direction (enhancing vs. suppressive) of the effects of stress or stress hormones on immune function: (1) Duration (acute vs. chronic) of stress: Acute or short-term stress experienced at the time of immune activation can enhance innate and adaptive immune responses. Chronic or long-term stress can suppress immunity by decreasing immune cell numbers and function and/or increasing active immunosuppressive mechanisms (e.g. regulatory T cells). Chronic stress can also dysregulate immune function by promoting proinflammatory and type-2 cytokine-driven responses. (2) Effects of stress on leukocyte distribution: Compartments that are enriched with immune cells during acute stress show immunoenhancement, while those that are depleted of leukocytes, show immunosuppression. (3) The differential effects of physiologic versus pharmacologic concentrations of glucocorticoids, and the differential effects of endogenous versus synthetic glucocorticoids: Endogenous hormones in physiological concentrations can have immunoenhancing effects. Endogenous hormones at pharmacologic concentrations, and synthetic hormones, are immunosuppressive. (4) The timing of stressor or stress hormone exposure relative to the time of activation and time course of the immune response: Immunoenhancement is observed when acute stress is experienced at early stages of immune activation, while immunosuppression may be observed at late stages of the immune response. We propose that it is important to study and, if possible, to clinically harness the immunoenhancing effects of the acute stress response, that evolution has finely sculpted as a survival mechanism, just as we study its maladaptive ramifications (chronic stress) that evolution has yet to resolve. In view of the ubiquitous nature of stress and its significant effects on immunoprotection as well as immunopathology, it is important to further elucidate the mechanisms mediating stress-immune interactions and to meaningfully translate findings from bench to bedside.

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Bidirectional Effects of Corticosterone on Splenic T-Cell Activation: Critical Role of Cell Density and Culture Time

Cited by 13 publications

References 25 publications

Rimexolone inhibits proliferation, cytokine expression and signal transduction of human CD4+ T-cells

Rimexolone inhibits proliferation, cytokine expression and signal transduction of human CD4+ T-cells

Factors affecting reconstitution of the T cell compartment in allogeneic haematopoietic cell transplant recipients

Enhancing versus Suppressive Effects of Stress on Immune Function: Implications for Immunoprotection and Immunopathology

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