Thymocyte apoptosis induced by elevated endogenous corticosterone levels

Abstract

A well-known model of apoptosis is induction in thymocytes by injection of pharmacological doses of exogenous steroids. The aim of this study was to investigate whether this process also occurs under physiological conditions, i.e. by stimulation of endogenous glucocorticoid release, using the chicken as an experimental model. Endogenous glucocorticoid levels can be elevated by immunization with exogenous antigens or by injection of conditioned medium, e.g. supernatant of mitogen-stimulated spleen cells. This effect is mediated by so-called glucocorticoid-increasing factors, and is considered to act as an immunoregulatory principle. Thymocyte DNA of so treated birds showed a typical "ladder" pattern after electrophoresis in a 1.8% agarose gel, and degradation could be prevented by RU 38,486. This provides evidence that apoptosis can be induced by elevating endogenous corticosterone levels in vivo. By means of in situ nick translation (ISNT) and simultaneous immunofluorescence tests, it was possible to analyze various thymic subpopulations during apoptosis after treatment with exogenous glucocorticoids. Additionally, using confocal microscopical techniques, apoptosis of the same cells as analyzed by ISNT is shown. The possible role of elevated concentrations of endogenous glucocorticoids in regulating thymocyte cell death and autoimmune diseases is discussed.

Effects of T3Rα1 and T3Rα2 Gene Deletion on T and B Lymphocyte Development

“…The stress response influences the immune system, notably through glucocorticoid production, which down-regulates immune processes and induces apoptosis of lymphoid cells (25). In particular, the percentage of double-positive thymocytes is a good indicator of stress, as these cells are the most sensitive to glucocorticoid-induced depletion (26). Hence, to assess stress levels, we have measured cortisol levels in the blood of mice aged 18 or 32 days.…”

TCR signaling inhibits glucocorticoid-induced apoptosis in murine thymocytes depending on the stage of development

“…It is well known that GC induce apoptosis in immature thymocytes, an effect observed in vitro [10][11][12] as well as in vivo, either after injection of synthetic GC [13][14][15][16] or by the action of endogenous GC [17]. Conversely, removal of endogenous GC by adrenalectomy leads to hypertrophy of the thymus [18] and spleen [19].…”

T Cell Receptor Signaling Inhibits Glucocorticoid-induced Apoptosis by Repressing the SRG3 Expression via Ras Activation

“…GC sensitivity of thymocytes is developmentally regulated during maturation in the thymus. Immature CD4 ϩ CD8 ϩ double-positive (DP) thymocytes are known to be exquisitely susceptible to GC-induced apoptosis, whereas mature CD4 ϩ or CD8 ϩ single-positive (SP) T cells are relatively resistant (4,21). Thus, it is conceivable that the immature thymocytes to be positively selected should be protected from apoptotic actions of GCs.…”