The thymic education of developing T cells in self neuroendocrine principles

Geenen, Vincent; Robert, Françoise; Martens, Henri; Groote, Donat De; Franchimont, P

doi:10.1007/bf03344936

Cited by 19 publications

(13 citation statements)

References 85 publications

(58 reference statements)

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“…It will be also of interest to determine whether Abs against other thymic self-antigens such as neurokinin A [39] and insulin-like growth factor II [40,41] are also able to affect TEC secretory activity. At the present stage, this study supports our model on the dual physiological role played in T-cell differentiation by the thymic repertoire of neuroendocrine-related polypeptides [8,9].…”

Section: Discussionsupporting

confidence: 89%

“…The thymic repertoire of neuroendocrine-related polypeptide precursors has been proposed to recapitulate at the molecular level the dual physiologic role played by the thymus in T-cell development [8][9][10]. With a special regard to the neurohypophysial peptide family, our group as well as others have shown that thymic epithelial and nurse cells (TEC/TNC) synthesize oxytocin (OT) and its precursor-associated protein, OT-neurophysin [11,12].…”

Section: Introductionmentioning

confidence: 99%

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Cytokine production by human thymic epithelial cells: control by the immune recognition of the neurohypophysial self-antigen

Martens

Malgrange

Robert

et al. 1996

Regulatory Peptides

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Oxytocin (OT) has been shownto be the dominantpeptideof the neurohypophysial familyexpressedby thymicepithelialand nurse cells (TEC/TNC) invmiousspecies. Thymic OT is not secreted but, after translocation of a hybrid neurophysin/MHC class I protein,is integratedwithinthe plasmamembraneof TEC, thus allowing its presentation to pre-T cells. In order to further demonstrate that thymic OT behaves like a membrane antigen, we assessed the effect of rnAbs to OT on cytokine productions by cultures enriched in human TEC. 75-85% pure TEC cultures were prepared tlom human thymic fragments. Using immunofluorescence and confocal microscopy, ir-OT, ir-interleukin-1~(IL-1P), ir-interleukin-6 (IL-6) and ir-leukemia inhibitory factor (LIF) could be detected in these TEC cultures. ir-OT was restricted to TEC, while some ir-IL-6 and ir-LIF were also seen in occasional fibroblasts. In basal conditions, ir-IL-6 and ir-LIF (but not ir-OT and ir-IL-l@) were detected in the supematants of human TEC cultures. MAbs to OT induced a marked increase of ir-IL-6 and ir-LIF secretion in TEC cultures. No significant effect was observed using mAbs against vasopressin, mouse immunoglobulins, or control ascitic fluid controls. These data show that OT is fully processed and recognized by specific mAbs at the outer surface of TEC plasma membrane. They further support that thymic OT behaves as the self-antigen of the nenrohypophysial family.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Cytokine production by human thymic epithelial cells: control by the immune recognition of the neurohypophysial self-antigen

Martens

Malgrange

Robert

et al. 1996

Regulatory Peptides

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“…Since central T-cell tolerance of neuroendocrine functions could be induced by the thymic repertoire of neuroendocrine self-antigens, 21 a series of investigations was initiated in order to identify the dominant member of the insulin family expressed in the thymic microenvironment. Using a panel of specific antibodies directed against several members and epitopes of the insulin family, IR IGF-II was clearly identified within TEC of the subcapsular cortex and the medulla of human and rat thymus.…”

Section: Historical Overview Of Thymic Insulin-like Polypeptidesmentioning

confidence: 99%

The intrathymic expression of insulin-related genes: implications for pathophysiology and prevention of Type 1 diabetes

Geenen

Lefèbvre

1998

Diabetes Metab. Rev.

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Recent experimental work has challenged and shattered the old concept of a sequestration of pancreatic islet antigens from developing T-cells within the thymic environment. There is now compelling evidence that the central immunological tolerance of the whole insulin family may be induced during the process of T-cell ontogeny in the thymus. Transcripts of insulin-like growth factor II (IGF-II), IGF-I and insulin genes have been characterized in human, rat and mouse thymuses. At the peptide level, IGF-II was shown to be the dominant polypeptide of the insulin family in the thymus from different species. Data are presented which support a dual role of thymic IGF-II both in T-cell development as well as in T-cell negative selection. Using animal models of autoimmune diabetes, current research is investigating the hypothesis that a defect of thymic T-cell education to the insulin family is implicated in the pathophysiology of human Type 1 diabetes. An efficient and secure prevention of Type 1 diabetes could be designed on the basis of the strong natural tolerogenic properties of the thymus.

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“…Bien que certains mécanismes tolérogènes incomplets existent dans les sites héma-topoïétiques primaires (le foie et la moelle osseuse), la tolérance des cellules B dépendante de l'antigène est surtout secondaire à l'absence de coopération T. Dès lors, parmi toutes les struc- tures lymphoïdes, le thymus est l'unique organe spécialisé dans l'établissement de la tolérance du soi [5]. Le thymus n'est pas une glande endocrine, mais il est un point de rencontre crucial entre les systèmes immunitaire et neuroendocrine [6]. Dans cet organe responsable en premier lieu de la thymopoïèse (génération des cellules T et de la diversité du répertoire des TCR), le système neuroendocrine intervient dès les premières étapes du contrôle de la différenciation des lymphocytes T. De plus, les cellules T entreprennent dans le thymus un processus complexe d'éducation qui permet d'établir leur tolérance à l'égard des fonctions neuroendocrines.…”

Section: Introductionunclassified

Les cibles hormonales de la réponse auto-immune

Geenen

2008

Annales d'Endocrinologie

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors

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The thymic education of developing T cells in self neuroendocrine principles

Cited by 19 publications

References 85 publications

Cytokine production by human thymic epithelial cells: control by the immune recognition of the neurohypophysial self-antigen

Cytokine production by human thymic epithelial cells: control by the immune recognition of the neurohypophysial self-antigen

The intrathymic expression of insulin-related genes: implications for pathophysiology and prevention of Type 1 diabetes

Les cibles hormonales de la réponse auto-immune

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