Age-associated changes in CD90 expression on thymocytes and in TCR-dependent stages of thymocyte maturation in male rats

Leposavić, Gordana; Pešić, Vesna; Kosec, Duško; Radojević, Katarina; Arsenović-Ranin, Nevena; Pilipović, Ivan; Perišić, Milica; Plećaš-Solarović, Bosiljka

doi:10.1016/j.exger.2006.03.006

Cited by 22 publications

(46 citation statements)

References 67 publications

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“…Although thymic weight in 10-monthold rats did not differ from values for 4-and 7-month-old animals, the total number of thymocytes in both thymic compartments, and hence the overall organ cellularity, were significantly reduced reflecting, most likely, an age-associated increase in thymocyte sensitivity to apoptotic stimuli followed by decreased responsiveness to proliferative signaling. This assumption emerged from our findings obtained with thymocyte cultures, which are fully consistent with previously reported data on cell sensitivity to apoptotic and proliferative signaling in thymocyte cultures from aged Wistar rats (14). The ageassociated expansion of connective-adipose tissue described here, which compensates for the loss of lymphoid tissue, has also been observed in aged male Wistar rats (24).…”

Section: Discussionsupporting

confidence: 92%

“…These cell suspensions were washed in ice-cold complete RPMI-1640 medium, and the number of cells in each of them was enumerated using an improved Neubauer hemocytometer. As expected (14), the total number of thymocytes/thymus thus estimated did not significantly differ from the corresponding value measured morphometrically. The viability of cell preparations (as determined by Trypan blue exclusion) was routinely greater than 95%.…”

Section: Preparation Of Thymocyte Suspensionssupporting

confidence: 80%

“…As previously described (14), 100 µL RPMI 1640 with 5 µg/mL concanavalin A (ConA, Sigma-Aldrich Chemie, Taufkirchen, Germany) was added to 100 µL of a cell suspension containing 2.5 x 10 5 thymocytes dispersed into plastic 96-well plates (Nunc A/S, Roskilde, Denmark) to attain a final ConA concentration of 2.5 µg/mL. All cultures were run in triplicate.…”

Section: Analysis Of Cycling Cellsmentioning

confidence: 99%

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Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats

Pesić¹,

Radojević²,

Kosec³

et al. 2007

Braz J Med Biol Res

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The role of gonadal hormones in induction and, particularly, maintenance/progression of rat thymic involution, which normally starts around puberty, was reassessed by examining the effects of peripubertal orchidectomy on thymic weight and morphometric parameters at different times up to the age of 10 months. Up to 6 months postcastration both thymic weight and cellularity in orchidectomized (Cx) rats were greater than in age-matched control rats, sham Cx (Sx). The increase in thymic cellularity reflected an increase in thymocyte proliferation rate (the proportion of proliferating cells was 18.6 ± 0.7% in 2-month-old Cx (N = 5) vs 13.4 ± 0.3% (N = 5) in age-matched Sx rats) followed by reduced sensitivity to apoptotic signals (apoptotic thymocytes were 9.8 ± 0.9% in 2-month-old Cx (N = 5) vs 15.5 ± 0.3% (N = 5) age-matched Sx rats). However, 9 months post-orchidectomy, neither thymic weight and cellularity nor any of the morphometric parameters analyzed differed between Cx and control rats. The reduction of thymic cellularity in Cx rats to control values may be related to increased sensitivity of their thymocytes to apoptotic signals in culture (72.6 ± 1.2% in 10-month-old vs 9.8 ± 0.9% in 2-month-old Cx rats) followed by reduced responsiveness to proliferative stimuli (14.1 ± 0.2% in 10-month-old vs 18.6 ± 0.7% in 2-month-old Cx rats). Thus, the study indicates that the effects of peripubertal orchidectomy on thymic weight and cellularity, as well as on the main morphometric indices, are long-lasting but not permanent, i.e., that removal of the testes can only postpone but not prevent age-related organ atrophy and consequently functional deterioration of the immune system.

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Section: Discussionsupporting

confidence: 92%

Section: Preparation Of Thymocyte Suspensionssupporting

confidence: 80%

Section: Analysis Of Cycling Cellsmentioning

confidence: 99%

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Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats

Pesić¹,

Radojević²,

Kosec³

et al. 2007

Braz J Med Biol Res

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“…In the thymus, catecholamines inhibit T-lymphocyte development, acting via a-and b-adrenoreceptors (a-AR and b-AR) on the surface of developing lymphoid and nonlymphoid cells (reviewed in Leposavic et al 2006Leposavic et al , 2008. Effects of catecholamines on T-lymphocyte development may be modulated by glucocorticoids (Pilipovic et al 2010).…”

Section: Catecholaminesmentioning

confidence: 99%

Interpreting Stress Responses during Routine Toxicity Studies

et al. 2013

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Stress often occurs during toxicity studies. The perception of sensory stimuli as stressful primarily results in catecholamine release and activation of the hypothalamic-pituitary-adrenal (HPA) axis to increase serum glucocorticoid concentrations. Downstream effects of these neuroendocrine signals may include decreased total body weights or body weight gain; food consumption and activity; altered organ weights (e.g., thymus, spleen, adrenal); lymphocyte depletion in thymus and spleen; altered circulating leukocyte counts (e.g., increased neutrophils with decreased lymphocytes and eosinophils); and altered reproductive functions. Typically, only some of these findings occur in a given study. Stress responses should be interpreted as secondary (indirect) rather than primary (direct) test article-related findings. Determining whether effects are the result of stress requires a weight-of-evidence approach. The evaluation and interpretation of routinely collected data (standard in-life, clinical pathology, and anatomic pathology endpoints) are appropriate and generally sufficient to assess whether or not changes are secondary to stress. The impact of possible stress-induced effects on data interpretation can partially be mitigated by toxicity study designs that use appropriate control groups (e.g., cohorts treated with vehicle and subjected to the same procedures as those dosed with test article), housing that minimizes isolation and offers environmental enrichment, and experimental procedures that minimize stress and sampling and analytical bias.This article is a comprehensive overview of the biological aspects of the stress response, beginning with a Summary (Section 1) and an Introduction (Section 2) that describes the historical and conventional methods used to characterize acute and chronic stress responses. These sections are followed by reviews of the primary systems and parameters that regulate and/or are influenced by stress, with an emphasis on parameters evaluated in toxicity studies:

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“…Therefore, with ageing, the thymic tissue weakens as a source of naïve T lymphocytes (Romanyukha and Yashin, 2003). The reduced T cell output, together with an increase in apoptosis of naïve T-cells limits the ability of aged individuals to respond to newly encountered antigens (Leposavic et al, 2006). The markedly reduced size of the naïve T-cell subpopulation together with an increased number of memory cells in the periphery, is a clear-cut characteristic of ageing in the immune cells (Romanyukha and Yashin, 2003).…”

Section: Peripheral Blood Mononuclear Cellsmentioning

confidence: 99%

Evaluation of Immunomodulatory Effect: Selection of the Correct Targets for Immunostimulation Study

Chun-Chu¹

2011

American Journal of Immunology

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Problem statement: Numerous plants or remedies that are traditionally used for various diseases had been claimed to maintain general good health, particularly the immune system. With the advanced understanding on immunology and ethnopharmacology, study on the interaction of this herb with the immune system is critical to understand the safety and its efficacy as a potent immunomodulatory agent. Approach: Selecting proper immune cells from a suitable immune organ allowed for the understanding on the mode of immunomodulation. Lymphocytes isolated from mammalian thymus, spleen and bone marrow represented great candidates for this immunomodulatory study. Results: A number of herbal extracts including that of Rhaphidophora korthalsii and compounds isolated from this plant, namely lectin and zerumbone, had been identified as potent immunostimulators. Conclusion/Recommendations: Future studies are needed to elucidate the mechanism underlaying activites of these immunomodulatory agents.

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Age-associated changes in CD90 expression on thymocytes and in TCR-dependent stages of thymocyte maturation in male rats

Cited by 22 publications

References 67 publications

Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats

Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats

Interpreting Stress Responses during Routine Toxicity Studies

Evaluation of Immunomodulatory Effect: Selection of the Correct Targets for Immunostimulation Study

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