Tyrosine kinase activation in thymic epithelial cells: necessity of thymocyte contact through the gp23/45/90 adhesion complex

Coutrure, Clément; Amarante-Mendes, Gustavo P.; Potworowski, Édouard F.

doi:10.1002/eji.1830221017

Cited by 18 publications

(5 citation statements)

References 33 publications

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“…A second type of medullary epithelial cell expresses high levels of MHC class 11 or class I, B7 molecules [5, Development of cortical and medullary cell types requires the presence of thymocytes which were shown to provide organizing [ 131 or growth-promoting signals [ 151. In vitro, activation [32] or growth [33] of medullary stromal cell lines can be modulated by thymocytes. Our results show that the development of two medullary epithelial cell subsets is not synchronous.…”

Section: Discussionmentioning

confidence: 99%

Thymocytes and RelB‐dependent medullary epithelial cells provide growth‐promoting and organization signals, respectively, to thymic medullary stromal cells

et al. 1997

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The thymic medulla is composed of distinct epithelial cell subsets, defined in this report by the reactivity of two novel antibodies, 95 and 29, raised against mouse thymic epithelial cell lines. These antibodies were used to probe the development of medulla in wild-type or mutant thymuses. In CD3 epsilon-deficient mice where thymocyte maturation is arrested at the CD4- CD8- stage, few scattered 95+ and 29+ epithelial cells are found. When few mature thymocytes develop as in CD3- zeta/eta mice, expansion and organization of 95+ but not 29+ cells, becomes detectable. In RelB-deficient mice, T cell maturation proceeds normally but negative selection is inefficient due to the lack of thymic medulla and dendritic cells. Strikingly, 29+ epithelial cells are absent and 95+ medullary epithelial cells are scattered throughout the thymus, intermingling with CDR1+ cortical epithelium. In chimeric mice lacking only dendritic cells, the corticomedullary junction persists and both 95+ and 29+ epithelial cells are localized in the medulla. These results suggest that two types of signals are required for development of thymic medulla. A growth signal depends upon the presence of maturing thymocytes, but organization of the thymic medulla requires the presence of activated 29+ medullary epithelial cells.

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Section: Discussionmentioning

confidence: 99%

Thymocytes and RelB‐dependent medullary epithelial cells provide growth‐promoting and organization signals, respectively, to thymic medullary stromal cells

et al. 1997

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“…Although the func tion o f the medullary epithelium is unclear, clonal deletion is manifest in this region (even if induced in the cortex) and the epithelium can induce tolerance in the form o f anergy [24][25][26]. Medullary epithelium also forms stromal cell complexes with thymocytes which may be maturation link ed [27,28] and possibly related to emigration [29][30][31][32][33].…”

Section: Discussionmentioning

confidence: 99%

The Murine Thymic Microenvironment: Changes with Age

Takeoka

Chen

Yago

et al. 1996

Int Arch Allergy Immunol

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Immunosenescence has been well described in both human and a variety of animal species and has an important influence on changes in immune function. Although several mechanisms may be operating to explain the alterations in immune function with age, one factor that has attracted significant attention has been the progressive age-dependent involution of the thymus. Hitherto, most studies of thymus have focused only on thymocytes. We have now taken advantage of a well-defined panel of monoclonal antibodies (mAbs called MTS) that recognize and characterize the thymic miroenvironment, including epithelial and nonepithelial elements. Recent data using these MTS mAbs have disclosed significant abnormalities in the thymic cortex in models of murine lupus including the unusual appearance of medullary-type epithelial cells in the cortical areas and the presence of epithelial free spaces or ‘cortical holes’. In this study, we investigated age-related changes in the thymic microenvironment in 12-month-old C3H/HeJ, C57BL/6 and BALB/c mice. Controls included thymus from young 4-to 6-week-old mice as well as 6-month-old BALB/c mice. As expected, the thymus of all 12-month-old mice manifested normal and distinctive separation of cortical and medullary epithelium. However, unlike younger mice, the 12-month-old mice had severe changes in these regions. For example, in older mice, the cortex and medulla were diffusely irregular and atrophic and had a poorly defined cortico medullary junction; the former having small disrupted epithelial networks, and the latter containing clusters of atrophic cells. Moreover, the extracellular matrix was increased and contained large irregularly shaped clusters. Interestingly, the thymus of 6-month-old mice expressed some changes within the medullary epithelium and the extracellular matrix, but the cortical epithelium remained unchanged. These age-related degenerative changes in the thymic microenvironment differ significantly from the abnormalities identified in autoimmunity and may be a factor in immunosenescence.

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“…Of importance here is that influences may come from mesenchymal ''passenger'' leukocytes that influence the organization of the thymic stationary microenvironment (Palmer et al, 1993). In vitro studies have shown that lymphocytes induce protein phosphorylation (Couture et al, 1992) and marker expression in cultured epithelial cells (Small et al, 1989). Interestingly, this epithelial differentiation can be induced not only by T cells bearing the ab-T-cell receptor (representing the major population of lymphocytes in the normal thymus), but also by T cells bearing the gd-T-cell receptor: in mice transgenic for a Vg-T-cell receptor, Ferrick et al (1990) even have observed a medullary hyperplasia.…”

Section: Introductionmentioning

confidence: 99%

Thymic microenvironment at the light microscopic level

Schuurman

Kuper

Kendall

1997

Microsc. Res. Tech.

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The thymus is a primary lymphoid organ that serves the immune system by providing an optimal microenvironment for developing T cells to rearrange the genes encoding the T‐cell receptor and to undergo positive and negative selection in shaping the peripheral T‐cell repertoire. The microenvironment of the organ is peculiar among lymphoid organs, as the supporting stroma consists of reticular epithelial cells. Bone marrow‐derived interdigitating cells and macrophages are the main accessory cell populations. The epithelium, interdigitating cells, and macrophages each contribute to the T‐cell selection process. During the last decade knowledge has been gathered that these cell populations show a considerable heterogeneity, as documented for subcellular features and immunologic phenotype. This heterogeneity may reflect various stages in differentiation, but may otherwise be linked to the functional activity of the cells. The authors survey the major cell populations, i.e., epithelial cells and lymphocytes. Macrophages and interdigitating cells are briefly discussed. Emphasis is given to functional aspects of histologic/cytologic features. Microsc. Res. Tech. 38:216–226, 1997. © 1997 Wiley‐Liss, Inc.

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Tyrosine kinase activation in thymic epithelial cells: necessity of thymocyte contact through the gp23/45/90 adhesion complex

Cited by 18 publications

References 33 publications

Thymocytes and RelB‐dependent medullary epithelial cells provide growth‐promoting and organization signals, respectively, to thymic medullary stromal cells

Thymocytes and RelB‐dependent medullary epithelial cells provide growth‐promoting and organization signals, respectively, to thymic medullary stromal cells

The Murine Thymic Microenvironment: Changes with Age

Thymic microenvironment at the light microscopic level

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