Age‐dependent changes in thymic macrophages and dendritic cells

Varas, Alberto; Sacedón, Rosa; Hernández-López, Carmen; Jiménez, Eva; García‐Ceca, Javier; Arias-Dı́az, Javier; Zapata, A.; Vicente, Ángeles

doi:10.1002/jemt.10411

Cited by 46 publications

(37 citation statements)

References 107 publications

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“…In the present study, we observe numerous thymic nurse cells in normal full-term newborn baboons in spite of physiologic cortical involution, similar to the persistence of thymic dendritic cells during normal thymic involution (52). Thus, the reduction in thymic nurse cells in 125-d/ PRN animals appears to be a pathologic condition, suggesting that thymic nurse cells do not survive during involution associated with injury, infection, or stress.…”

Section: Discussionmentioning

confidence: 69%

Accelerated Thymic Maturation and Autoreactive T Cells in Bronchopulmonary Dysplasia

Rosen

Lee

Cuttitta

et al. 2006

Am J Respir Crit Care Med

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Rationale: Bronchopulmonary dysplasia (BPD), a chronic lung disease of newborns triggered by oxygen and barotrauma, is characterized by arrested alveolarization. Increased levels of bombesinlike peptides shortly after birth mediate lung injury: anti-bombesin antibody 2A11 protects against BPD in two baboon models. The role of adaptive immunity in BPD has not been explored previously. Objectives: Our goal was to test the hypothesis that thymic architecture and/or T-cell function is altered with BPD, leading to autoimmunity and immunodeficiency. Methods: Thymic structure was analyzed by histopathology of thymic architecture and immunohistochemistry for thymic maturation markers (terminal deoxynucleotidyl transferase, proliferating cell nuclear antigen, CD4, and CD8). Thymic cortical epithelial cells (nurse cells) were studied using HLA-DR and protein gene product 9.5 as markers. Functional analysis was performed with "mixed lymphocyte reaction" of thymocyte or splenocyte responder cells with autologous lung cells as the stimulators. Measurements and Main Results: 2A11 treatment attenuates thymic cortical involution in BPD animals, sustaining terminal deoxynucleotidyl transferase-positive prothymocytes and thymocyte proliferation. BPD animals have increased CD4؉ cells in thymic cortex and lung interstitium, which are reduced by 2A11. Conversely, cortical protein gene product 9.5/HLA-DR-positive thymic nurse cells are depleted in BPD animals, but are preserved by 2A11-treatment. Whereas fetal thymocytes and splenocytes respond to phythemagglutinin/ionomycin and to a lesser extent, to autologous lung, BPD thymocytes and splenocytes are phythemagglutinin/ionomycinunresponsive, and yet react strongly to autologous lung. The 2A11 normalizes these responses. Conclusions: These observations suggest that bombesin-like peptides mediate premature thymic maturation and thymic nurse-cell depletion, leading to autoreactive T cells that could contribute to lung injury.

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Section: Discussionmentioning

confidence: 69%

Accelerated Thymic Maturation and Autoreactive T Cells in Bronchopulmonary Dysplasia

Rosen

Lee

Cuttitta

et al. 2006

Am J Respir Crit Care Med

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“…Zavala and Cavicchia (2006) observed changes in both morphology and expression (density) of CD1a on LCs in gingival epithelium from elderly subjects. Varas et al (2003) observed that thymic stromal DCs were only slightly affected by age. Increased inflammatory activity accompanies normal aging brain.…”

Section: Numbers Phenotype and Differentiationmentioning

confidence: 98%

Dendritic cells in human aging

Agrawal

Gupta

2007

Experimental Gerontology

100

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“…However, while the Sirpa 1 cDC decrease in proportion in the spleen, they increase in proportion in the ageing thymus. Previous studies have not investigated the changes in DC subsets in the ageing mouse thymus, whereas in the ageing human thymus it has been reported that there is a decrease in total thymic DC numbers, 48,49 but no change in their relative proportion. 49 Although in these studies the different subsets of human thymic DC were not defined, in general they are consistent with the results from our studies, where the predominant DC population in the thymus, the CD8a 1 cDC, also decreases in numbers but not in proportion until after middle age.…”

Section: Discussionmentioning

confidence: 95%

Regeneration of dendritic cells in aged mice

et al. 2010

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Age-related thymic involution causes a decreased output of thymocytes from the thymus, thereby resulting in impairment of T cell-mediated immunity. While alterations in the T cell and non-haematopoietic stromal compartments have been described, the effects of thymic involution on thymic dendritic cells (DC) are not clearly known. Thymic DC play an essential role in shaping T cell-mediated immune responses by deleting self-reactive thymocytes to establish central tolerance and by inducing regulatory T-cell (Treg) development. It is therefore important to assess the prevalence of and alterations to thymic DC with age, as this may impact on their function. We assessed the numbers and proportions of the three distinct subsets of thymic DC in ageing mice, and showed that these subsets are differentially regulated. This is expected as thymic DC subsets have different origins of development. We further assessed the responses of thymic DC in a regenerative environment, such as that induced by sex-steroid ablation (SSA), and clearly showed that, consistent with global thymus regrowth, all three DC populations increased in numbers and regained their relative proportions to thymocytes after an initial lag period. These findings are important for the clinical translation of thymic regenerative approaches, and indicate that SSA facilitates the maintenance of critical processes such as negative selection and Treg induction through promoting thymic DC regeneration. INTRODUCTIONThe thymus has a central role in the deterioration of the immune system with age due to its natural involution.1 Some thymic decline is initially apparent from as early as the first year in humans, but then thymus undergoes more pronounced degeneration from puberty such that by ,25 years of age, the thymus has decreased to approximately 50% of its size at birth progressing through to ,10% capacity by the fifth and sixth decades.2 While the mechanisms of thymic involution have not been precisely defined, there is a clear correlation with the influence of sex steroids, the removal of which reverses thymic atrophy in animal models. 1,[3][4][5][6][7][8] The progressive decrease in thymus size with age is associated with a loss in thymic epithelial cells and a concomitant decrease in thymopoiesis 9 leading to a reduced thymic output of naive T cells.

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Age‐dependent changes in thymic macrophages and dendritic cells

Cited by 46 publications

References 107 publications

Accelerated Thymic Maturation and Autoreactive T Cells in Bronchopulmonary Dysplasia

Accelerated Thymic Maturation and Autoreactive T Cells in Bronchopulmonary Dysplasia

Dendritic cells in human aging

Regeneration of dendritic cells in aged mice

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