Thymic nurse cells provide microenvironment for secondary T cell receptor α rearrangement in cortical thymocytes

Nakagawa, Yasushi; Ohigashi, Izumi; Nitta, Takeshi; Sakata, Masayo; Tanaka, Keiji; Murata, Shigeo; Kanagawa, Osami; Takahama, Yousuke

doi:10.1073/pnas.1213069109

Cited by 78 publications

(72 citation statements)

References 44 publications

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“…Thus, it seems that TNC formation is not essential for T cell development per se , but may result from lengthy ‘audition’ events that occur when only a small subset of DP thymocytes meets the positive selection criteria. Consistent with this, in non-TCR transgenic mice, TNCs were enriched in thymocytes harbouring secondary TCRα rearrangements 2 . Whether such unusual selection niches are indeed required to promote thymocyte survival and/ or continued TCR rearrangements remains to be shown.…”

Section: Cortical Epithelial Cellssupporting

confidence: 68%

“…In addition, individual cTECs can form multi-cellular complexes that encompass up to 20 thymocytes and are referred to as thymic nurse cells (TNCs). TNC numbers are decreased in TCR-transgenic mice, possibly as a consequence of ‘facilitated’ transit of thymocytes through β-selection and positive selection 2 . Thus, it seems that TNC formation is not essential for T cell development per se , but may result from lengthy ‘audition’ events that occur when only a small subset of DP thymocytes meets the positive selection criteria.…”

Section: Cortical Epithelial Cellsmentioning

confidence: 99%

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Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see)

et al. 2014

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The fate of developing T cells is specified by interactions of their antigen receptor with self-peptide/MHC complexes displayed by thymic antigen presenting cells (APCs). Various thymic APCs subsets are strategically positioned in particular thymic microenvironments and orchestrate the selection of a functional and self-tolerant T cell repertoire. Here, we will review the different strategies that these APCs employ to sample and process self-antigens and thereby generate partly unique, ‘idiosyncratic’ peptide/MHC ligandomes. We will discuss how the particular composition of these APC-subset-specific peptide/MHC ligandomes not only shapes the T cell repertoire in the thymus, but may also indelibly imprint the behavior of mature T cells in the periphery.

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Section: Cortical Epithelial Cellssupporting

confidence: 68%

Section: Cortical Epithelial Cellsmentioning

confidence: 99%

Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see)

et al. 2014

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“…6A-D). Other TEC related multicellular structures that could be depicted infrequently by neurofilament staining seem to be thymic nurse cell aggregates (TNC), described as structures built of TEC together with thymocytes and other cell types but unknown function [61,62]. Again, the morphology of the neurofilament signal associated with TNC was different from the phenomenon seen with the nTEC at the corticomedullary junction.…”

Section: Thymus and A Possible Neuro-epithelial Entrance Sitementioning

confidence: 98%

Neural architecture in lymphoid organs: Hard‐wired antigen presenting cells and neurite networks in antigen entrance areas

Wülfing¹,

Schuran²,

Urban³

et al. 2018

Immunity Inflam & Disease

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IntroductionRecently, we found abundant innervation of antigen presenting cells that were reached and enclosed by single neurites. These neurally hard‐wired antigen presenting cells (wAPC) could be observed in the T‐cell zone of superficial cervical lymph nodes of rats and other mammalians, including humans.MethodsAs a consequence, we investigated lymph nodes at many different anatomical positions as well as all primary and secondary lymphoid organs (SLO) in rodents for a similar morphology of innervation regarding antigen presenting cells known in those tissues.ResultsAs a result, we confirmed wAPC in lymph nodes independent from their draining areas and anatomical positions but also in all other T‐cell zones of lymphoid organs, like Peyer's patches, NALT and BALT, as well as in the thymic medulla. Other cells were innervated in a similar fashion but with seemingly missing antigen presenting capacity. Both types of innervated immune cells were observed as being also present in the dermis of the skin. Only in the spleen wAPC could not be detected. Beyond this systematic finding, we also found another regular phenomenon: a dense network of neurites that stained for neurofilament always in antigen entrance areas of lymphoid organs (subsinoidal layer of lymph nodes, subepithelial dome of Peyer's patches, subsinoidal layer of the splenic white pulp, margins of NALT and BALT). Lastly, also thymic epithelial cells (TEC) restricted to the corticomedullary junction of the thymus showed similar neurofilament staining.ConclusionsTherefore, we propose much more hard‐wired and probably afferent connections between lymphoid organs and the central nervous system than is hitherto known.

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“…Recently, Takahama and colleagues revisited the isolation and characteristics of TNCs. They identified such cells on the basis of preferential staining for CD45 only after membrane permeabilization 35 . They also described "broken" TNC in their preparation, which consisted of a cTEC and multiple bound thymocytes.…”

Section: Discussionmentioning

confidence: 99%

Isolation, Identification, and Purification of Murine Thymic Epithelial Cells

Xing

Hogquist

2014

JoVE

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The thymus is a vital organ for T lymphocyte development. Of thymic stromal cells, thymic epithelial cells (TECs) are particularly crucial at multiple stages of T cell development: T cell commitment, positive selection and negative selection. However, the function of TECs in the thymus remains incompletely understood. In the article, we provide a method to isolate TEC subsets from fresh mouse thymus using a combination of mechanical disruption and enzymatic digestion. The method allows thymic stromal cells and thymocytes to be efficiently released from cellcell and cell-extracellular matrix connections and to form a single-cell suspension. Using the isolated cells, multiparameter flow cytometry can be applied to identification and characterization of TECs and dendritic cells. Because TECs are a rare cell population in the thymus, we also describe an effective way to enrich and purify TECs by depleting thymocytes, the most abundant cell type in the thymus. Following the enrichment, cell sorting time can be decreased so that loss of cell viability can be minimized during purification of TECs. Purified cells are suitable for various downstream analyses like Real Time-PCR, Western blot and gene expression profiling. The protocol will promote research of TEC function and as well as the development of in vitro T cell reconstitution. Video LinkThe video component of this article can be found at

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Thymic nurse cells provide microenvironment for secondary T cell receptor α rearrangement in cortical thymocytes

Cited by 78 publications

References 44 publications

Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see)

Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see)

Neural architecture in lymphoid organs: Hard‐wired antigen presenting cells and neurite networks in antigen entrance areas

Isolation, Identification, and Purification of Murine Thymic Epithelial Cells

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