Phenotypical and morphological changes in the thymic microenvironment from ageing mice

Aw, Danielle; Taylor‐Brown, Frances; Cooper, Kate; Palmer, Donald B.

doi:10.1007/s10522-008-9182-2

Cited by 37 publications

(26 citation statements)

References 48 publications

(65 reference statements)

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“…Accordingly, the medullary area was proportionally increased but also appeared importantly altered. Other authors have described similar features in the involuted thymuses during aging, including significant reduction of the thymic surface area, decline of MHC class II and keratin expression and increased presence on certain molecules, such as Notch1 and Delta [6] . The condition of thymic medulla during aging is controversial.…”

Section: Morphological Changes In the Human Thymus During Agingmentioning

confidence: 58%

“…The condition of thymic medulla during aging is controversial. Some authors have described fewer changes in the medulla than in the thymic cortex of aged thymuses, but others suggest a parallel decline of both thymic compartments [6] . Retraction of epithelial cell processes in all thymic compartments also occurred in the older thymuses, a feature that has been related with the appearance of epithelial-free areas in the involuted thymuses [6] .…”

Section: Morphological Changes In the Human Thymus During Agingmentioning

confidence: 99%

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The CXCL12/CXCR4 Pair in Aged Human Thymus

Hernández-López

Varas²,

Sacedón³

et al. 2010

Neuroimmunomodulation

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CXCL12 is an important CXC chemokine involved in numerous biological processes. We had previously demonstrated the synergistic participation of CXCL12 and IL-7 in the control of both survival and proliferation of CD34⁺ human thymic lymphoid progenitors. On this basis, we hypothesize a presumptive role for CXCL12 and its receptor, CXCR4, in the thymus involution. In this respect, in the current report we describe the expression of both molecules in the human thymus during aging. Our results demonstrate that, despite the profound alterations observed in the thymic epithelial microenvironment of aged thymuses, the proportions of different CD4/CD8 thymocyte subsets do not undergo significant variations. Remarkably, a strong CXCL12 expression was found in older thymuses, which appeared in the same locations as in younger thymuses: the subcapsulary and medullary areas. The proportions of CXCR4⁺ cells, most of them belonging to the CD3^– compartment, showed no important variations in the older thymuses. However, within the CD34⁺ cell population, a significant reduction in the expression of CXCR4 molecules was observed.

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Section: Morphological Changes In the Human Thymus During Agingmentioning

confidence: 58%

Section: Morphological Changes In the Human Thymus During Agingmentioning

confidence: 99%

The CXCL12/CXCR4 Pair in Aged Human Thymus

Hernández-López

Varas²,

Sacedón³

et al. 2010

Neuroimmunomodulation

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“…13,14 However, given the essential role that the microenvironment plays in the development and activation of many immune cell types, 15,16 changes in the tissue architecture may also contribute towards immunosenescence. 17 Indeed, we and others have observed that regression of the thymus is accompanied by significant alterations of the thymic microenvironment, [18][19][20][21] and such changes are believed to contribute towards the reduced thymic function that is observed in the aged. [22][23][24] The spleen is a secondary lymphoid organ that is responsible for initiating immune responses to bloodborne antigens.…”

Section: Introductionmentioning

confidence: 95%

Disorganization of the splenic microanatomy in ageing mice

Hilliard

Nishikawa

et al. 2016

Immunology

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SummaryThe precise mechanisms responsible for immunosenescence still remain to be determined, however, considering the evidence that disruption of the organization of primary and secondary lymphoid organs results in immunodeficiency, we propose that this could be involved in the decline of immune responses with age. Therefore, we investigated the integrity of the splenic microarchitecture in mice of increasing age and its reorganization following immune challenge in young and old mice. Several differences in the anatomy of the spleen with age in both the immune and stromal cells were observed. There is an age-related increase in the overall size of the white pulp, which occurs primarily within the T-cell zone and is mirrored by the enlargement of the T-cell stromal area, concurrent to the distinct boundary between T cells and B cells becoming less defined in older mice. In conjunction, there appears to be a loss of marginal zone macrophages, which is accompanied by an accumulation of fibroblasts in the spleens from older animals. Furthermore, whereas the reorganization of the white pulp is resolved after several days following antigenic challenge in young animals, it remains perturbed in older subjects. All these age-related changes within the spleen could potentially contribute to the age-dependent deficiencies in functional immunity.

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“…Immunofluorescence on tissue sections of thymi from 4 mo old C57BL/6 mice was carried out as described previously (32). Sections were incubated sequentially with anti-BTN sera, or appropriate negative control serum, followed by a biotinylated rabbit anti-rat secondary Ab (Jackson ImmunoResearch Laboratories, Newmarket, U.K.) to detect anti-BTN1A1 Abs, or biotinylated swine anti-rabbit secondary Ab (DakoCytomation) to detect anti-BTN2A2 Abs.…”

Section: Immunohistological Studiesmentioning

confidence: 99%

BTN1A1, the Mammary Gland Butyrophilin, and BTN2A2 Are Both Inhibitors of T Cell Activation

Smith

Knezevic

Ammann

et al. 2010

The Journal of Immunology

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111

124

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Butyrophilin (BTN) genes encode a set of related proteins. Studies in mice have shown that one of these, BTN1A1, is required for milk lipid secretion in lactation, whereas butyrophilin-like 2 is a coinhibitor of T cell activation. To understand these disparate roles of BTNs, we first compared the expression and functions of mouse Btn1a1 and Btn2a2. Btn1a1 transcripts were not restricted to lactating mammary tissue but were also found in virgin mammary tissue and, interestingly, spleen and thymus. In confirmation of this, BTN1A1 protein was detected in thymic epithelial cells. By contrast, Btn2a2 transcripts and protein were broadly expressed. Cell surface BTN2A2 protein, such as the B7 family molecule programmed death ligand 1, was upregulated upon activation of T cells. We next examined the potential of both BTN1A1 and BTN2A2 to interact with T cells. Recombinant Fc fusion proteins of murine BTN2A2 and, surprisingly BTN1A1, bound to activated T cells, suggesting the presence of one or more receptors on these cells. Immobilized BTN-Fc fusion proteins, but not MOG-Fc protein, inhibited the proliferation of CD4 and CD8 T cells activated by anti-CD3. BTN1A1 and BTN2A2 also inhibited T cell metabolism, IL-2, and IFN-γ secretion. Inhibition of proliferation was not abrogated by exogenous IL-2 but could be overcome following costimulation with high levels of anti-CD28 Ab. These data are consistent with a coinhibitory role for mouse BTNs, including BTN1A1, the BTN expressed in the lactating mammary gland and on milk lipid droplets.

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Phenotypical and morphological changes in the thymic microenvironment from ageing mice

Cited by 37 publications

References 48 publications

The CXCL12/CXCR4 Pair in Aged Human Thymus

The CXCL12/CXCR4 Pair in Aged Human Thymus

Disorganization of the splenic microanatomy in ageing mice

BTN1A1, the Mammary Gland Butyrophilin, and BTN2A2 Are Both Inhibitors of T Cell Activation

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