Questionable Thymic Nurse Cell

Pezzano, Mark; Samms, Michael; Martinez, Marcia; Guyden, J.

doi:10.1128/mmbr.65.3.390-403.2001

Cited by 35 publications

(24 citation statements)

References 57 publications

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“…TNC is defined as a large epithelial cell that completely envelops many viable lymphoid cells within its intracellular vesicles (7)(8)(9)(10). Despite the initial suggestion that TNC may be important for T-cell development and selection, its in vivo existence has been questioned and its function has remained unclear (10,19,20). The present results, including the analysis of the intravital imaging results of β5t + cTECs, reveal that basketlike globular cTECs, including closed TNC complexes, are indeed present in the thymic cortex in situ and are not merely artificial structures formed during cell preparation.…”

Section: Discussionmentioning

confidence: 49%

“…It was further hypothesized that the TNC complex is a site for the positive and negative selection of T cells (16)(17)(18). However, how TNCs are involved in T-cell development, and selection has not been established (19). Whether TNCs are abundant in the thymic cortex (10) or derived from all parts of the thymus including the medulla (20) has not been clarified as well.…”

Section: Cd8mentioning

confidence: 99%

“…To further characterize the cTEC-thymocyte complexes, we next examined whether P1 open complexes and P2 TNC complexes were derived from cellular complexes that existed in the thymic cortex in vivo or were artificially formed in vitro during cell preparation after collagenase digestion, as previously suggested (10,19,20). Collagenase-digested thymic cells from C57BL/6 (B6) mice were mixed 1:1 with thymocytes prepared without enzyme digestion from B6.SJLPtprc a (B6-Ly5.1) congenic mice (Fig.…”

Section: Cd326mentioning

confidence: 99%

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

Nakagawa

Ohigashi

Nitta

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Distinct subsets of thymic epithelial cells (TECs) support T-cell development and selection. Isolated TECs contain multicellular complexes that enclose many viable thymocytes. However, the functions of those TECs, termed thymic nurse cells (TNCs), are unclear and the idea that TNCs are present in vivo is questioned. Here, we show that TNCs represent a fraction of cortical (c)TECs that are defined by the expression of thymoproteasomes. Intravital imaging revealed TNCs in the thymic cortex in situ, whereas TNCs were detected neither during embryogenesis nor in the postnatal thymuses of various "positiveselector" T-cell receptor (TCR)-transgenic mice, indicating that TNCs are not essential for T-cell differentiation, including positive selection. Rather, cells within TNCs were enriched for long-lived CD4 + CD8+ thymocytes that underwent secondary TCR-Vα rearrangement. Thus, TNC complexes are formed in vivo by persistent cTEC-thymocyte interactions that then provide a microenvironment that optimizes T-cell selection through secondary TCR rearrangement.repertoire selection | thymic microenvironment | beta5t

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Section: Discussionmentioning

confidence: 49%

Section: Cd8mentioning

confidence: 99%

Section: Cd326mentioning

confidence: 99%

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

Nakagawa

Ohigashi

Nitta

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…The expression of m17TLP is confirmed to a subset of TNC. As TNC have been found in two different areas of the thymus (reviewed in [33]), the outer cortex and the cortico-medullary junction, one may hypothesize that only the subset found at the cortico-medullary junction expresses m17TLP. Another explanation is that m17TLP is restricted to a particular developmental stage of TNC.…”

Section: Discussionmentioning

confidence: 99%

The human and mouse orthologous LIM-only proteins respectively encoded in chromosome 6 and 17 show a different expression pattern

Casrouge

Veitia

Kirchner

et al. 2004

Microbes and Infection

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Thymocytes interact with various subpopulations of thymic epithelial cells (TECs) at different stages of their development. To identify new molecules specifically expressed in TECs and/or thymic nurse cells (TNCs), we used representational difference analysis. We identified a LIM protein located on mouse chromosome 17 (m17TLP) and belonging to the family of the LIM-only proteins (LIMo). We found a new splice variant in addition to the two describedA and B isoforms. The three alternative species of m17TLP are found strictly in the thymic stroma. This protein is expressed on a subpopulation of TECs and TNCs. Strikingly, we found that the human ortholog of m17TLP, located on chromosome 6 (h6LIMo), is expressed in most tissues, but not in skeletal muscle. We have identified four human splice variants of h6LIMo which differ in their carboxy-terminal regions. The sequence comprising the genomic structure suggests that CRP2 is the closest known relative of m17TLP. Although the human and mouse nucleotide sequences are 88-97% homologous, this homology is reduced to 47% in the promoter regions, which strongly suggests that their differential expression is related to their promoter regulatory activity.

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“…A particular microenvironment of the thymus is formed by 2 cell types, thymic nurse cells (TNC), a TEC subtype, and immature thymocytes [for a review, see 15,16] . These complexes were first described in 1980 by Wekerle et al [17] and are observed both after isolation and in thymic sections [18,19] .…”

Section: Objectivementioning

confidence: 99%

Aire and Foxp3 Expression in a Particular Microenvironment for T Cell Differentiation

Hansenne

Louis

Martens

et al. 2008

Neuroimmunomodulation

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Objective: The thymus is the primary lymphoid organ responsible for T cell development and the establishment of central self-tolerance. Among thymic epithelial cells, thymic nurse cells (TNC) interact closely with immature thymocytes and constitute a special microenvironment for T cell differentiation and selection. In addition, TNC express neuroendocrine self-antigens such as oxytocin and insulin-like growth factor-2, whose intrathymic transcription is regulated by the autoimmune regulator gene/protein (Aire). Both effector and natural regulatory T cell (nTreg) lineages develop in the thymus, but the mechanisms leading to nTreg selection in the thymus are still unclear. Foxp3 is the most specific nTreg marker that is required for nTreg functional activity, but not for engagement into the Treg lineage. Aire has been suggested to be a potential factor implicated in this role. The objective of this study was to characterize Aire and Foxp3 expression in TNC/thymocyte complexes. Methods:Aire and Foxp3 expression was investigated by RT-qPCR in TNC/thymocyte complexes isolated by enzymatic digestion and sedimentation. Aire and Foxp3 proteins were located by confocal microscopy and specific immunocytochemistry. Results: Both Aire and Foxp3 transcripts were detected in TNC/thymocyte complexes. Foxp3 was detected in the nucleus of thymocytes internalized into TNC. Aire was located mainly in TNC cytoplasm and, although to a lower degree, in the nucleus of some TNC-associated thymocytes. Conclusions: Aire and Foxp3 are present in the particular TNC microenvironment which has previously been shown to support thymic selection. The differential localization of these two markers suggests a role for TNC in nTreg development.

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Questionable Thymic Nurse Cell

Cited by 35 publications

References 57 publications

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

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

The human and mouse orthologous LIM-only proteins respectively encoded in chromosome 6 and 17 show a different expression pattern

Aire and Foxp3 Expression in a Particular Microenvironment for T Cell Differentiation

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