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See detailDendritic cell differentiation and immune tolerance to insulin-related peptides in Igf2-deficient mice
Hansenne, Isabelle ULg; Renard-Charlet, C.; Greimers, Roland ULg et al

in Journal of Immunology (Baltimore, Md. : 1950) (2006), 176(8), 4651-4657

There is some evidence that insulin-like growth factor 2 (IGF-2) may intervene in the control of T cell differentiation. To further study the immunoregulatory function of this growth factor, we analyzed ... [more ▼]

There is some evidence that insulin-like growth factor 2 (IGF-2) may intervene in the control of T cell differentiation. To further study the immunoregulatory function of this growth factor, we analyzed the immune system of Igf2(-/-) mice. Phenotypically, some immunological parameters such as lymphoid organ morphology and cellularity were unaltered in Igf2(-/-) mice, but an increase of CD8(+) cells and a decrease of B220(+) cells were observed in spleen. In vitro, the development of bone marrow-derived dendritic cells was affected by the absence of Igf2 expression. After maturation, a higher percentage of immature dendritic cells was observed in Igf2(-/-) population, together with a secondary decrease in allogenic T cell proliferation. Activation of T cells was also affected by the lack of expression of this growth factor. The profile of B cell response in mutant mice immunized with IGF-2 evidenced a T-dependent profile of anti-IGF-2 Abs that was absent in Igf2(+/+) mice. The influence of IGF-2 upon tolerance to insulin was also assessed in this model, and this showed that IGF-2 also intervenes in tolerance to insulin. The presence of a T-dependent response in Igf2-deficient mice should allow cloning of specific "forbidden" T CD4(+) lymphocytes directed against IGF-2, as well as further investigation of their possible pathogenic properties against insulin family. [less ▲]

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See detailOntogenesis and functional aspects of oxytocin and vasopressin gene expression in the thymus network
Hansenne, Isabelle ULg; Rasier, G.; Pequeux, Christel ULg et al

in Journal of Neuroimmunology (2005), 158(1-2), 67-75

Ontogenesis of oxytocin (OT) and vasopressin (VP) gene expression and function were investigated in murine thymus. OT and VP transcripts were detected in the thymus on embryonic days 13 and 15 ... [more ▼]

Ontogenesis of oxytocin (OT) and vasopressin (VP) gene expression and function were investigated in murine thymus. OT and VP transcripts were detected in the thymus on embryonic days 13 and 15, respectively. Corresponding messenger RNAs were evidenced in thymic epithelial cells by in situ hybridization with a neurophysin probe. From all OT and VP receptors, only OTR was expressed by all T-cell subsets, while V1bR was found in double positive and single positive CD8 cells. In fetal thymic organ cultures, OTR antagonist d[DTyr(Et)(2), Thr(4)]OVT increased early apoptosis of CD8 cells, while V1bR antagonist (Sanofi SSR 149415) inhibited T-cell differentiation, and favored CD8 T-cell commitment. (C) 2004 Elsevier B.V. All rights reserved. [less ▲]

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See detailNouvelles donnees sur la pathogenie du diabete de type 1
Geenen, Vincent ULg; Brilot, F.; Louis, Céline ULg et al

in Revue Médicale de Liège (2005), 60(5-6, May-Jun), 291-6

The autoimmune nature of the diabetogenic process and the major contribution of T lymphocytes stand now beyond any doubt. However, despite the identification of the three major type 1-diabetes-related ... [more ▼]

The autoimmune nature of the diabetogenic process and the major contribution of T lymphocytes stand now beyond any doubt. However, despite the identification of the three major type 1-diabetes-related autoantigens (insulin, GAD65 and phosphatase IA-2), the origin of this immune dysregulation still remains unknown. More and more evidence supports a thymic dysfunction in the establishment of central self-tolerance to the insulin family as a crucial factor in the development of the autoimmune response selective of pancreatic insulin-secreting islet beta cells. All the genes of the insulin family (INS, IGF1 and IGF2) are expressed in the thymus network. However, IGF-2 is the dominant member of this family first encountered by T cells in the thymus, and only IGFs control early T-cell differentiation. IGF2 transcription is defective in the thymus in one animal model of type 1 diabetes, the Bio-Breeding (BB) rat. The sequence B9-23, one dominant autoantigen of insulin, and the homologous sequence B11-25 derived from IGF-2 exibit the same affinity and fully compete for binding to DQ8, one class-II major histocompatibility complex (MHC-II) conferring major genetic susceptibility to type 1 diabetes. Compared to insulin B9-23, the presentation of IGF-2 B11-25 to peripheral mononuclear cells (PBMCs) isolated from type 1 diabetic DQ8+ adolescents elicits a regulatory/tolerogenic cytokine profile (*IL-10, *IL-10/IFN-g, *IL-4). Thus, administration of IGF-2 derived self-antigen(s) might constitute a novel form of vaccine/immunotherapy combining both an antagonism for the site of presentation of a susceptible MHC allele, as well as a downstream tolerogenic/regulatory immune response. [less ▲]

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See detailNeurohypophysial Receptor Gene Expression by Thymic T Cell Subsets and Thymic T Cell Lymphoma Cell Lines
Hansenne, Isabelle ULg; Rasier, G.; Charlet-Renard, C. et al

in Clinical & Developmental Immunology (2004), 11(1), 45-51

Neurohypophysial oxytocin (OT) and vasopressin (VP) genes are transcribed in thymic epithelium, while immature T lymphocytes express functional neurohypophysial receptors. Neurohypophysial receptors ... [more ▼]

Neurohypophysial oxytocin (OT) and vasopressin (VP) genes are transcribed in thymic epithelium, while immature T lymphocytes express functional neurohypophysial receptors. Neurohypophysial receptors belong to the G protein-linked seven-transmembrane receptor superfamily and are encoded by four distinct genes, OTR, V1R, V2R and V3R. The objective of this study was to identify the nature of neurohypophysial receptor in thymic T cell subsets purified by immunomagnetic selection, as well as in murine thymic lymphoma cell lines RL12-NP and BW5147. OTR is transcribed in all thymic T cell subsets and T cell lines, while V3R transcription is restricted to CD4+CD8+ and CD8+ thymic cells. Neither V1R nor V2R transcripts are detected in any kind of T cells. The OTR protein was identified by immunocytochemistry on thymocytes freshly isolated from C57BL/6 mice. In murine fetal thymic organ cultures, a specific OTR antagonist does not modify the percentage of T cell subsets, but increases late T cell apoptosis further evidencing the involvement of OT/OTR signaling in the control of T cell proliferation and survival. According to these data, OTR and V3R are differentially expressed during T cell ontogeny. Moreover, the restriction of OTR transcription to T cell lines derived from thymic lymphomas may be important in the context of T cell leukemia pathogenesis and treatment. [less ▲]

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See detailQuantification of T cell receptor rearrangement excision circles to estimate thymic function: an important new tool for endocrine-immune physiology
Geenen, Vincent ULg; Poulin, J. F.; Dion, M. L. et al

in Journal of Endocrinology (2003), 176(3), 305-311

Although the thymus constitutes a target organ for most protein and steroid hormones, it has been quite difficult to determine the precise control exerted in vivo by the endocrine system upon thymic ... [more ▼]

Although the thymus constitutes a target organ for most protein and steroid hormones, it has been quite difficult to determine the precise control exerted in vivo by the endocrine system upon thymic function. The biological role of the thymus is to ensure the generation of a diversified population of peripheral T cells able to respond to non-self-antigens but nevertheless tolerant to self-antigens. For a long time, thymic function could not be monitored, as a consequence of the absence of adequate technology to differentiate recent thymic emigrants from naive T cells. The generation of T cell receptor (TCR) diversity occurs in the thymus through recombination of gene segments encoding the variable parts of the TCR alpha and beta chains. During these processes, by-products of the rearrangements are generated in the form of TCR excision circles (TRECs). As these molecules are lost upon further cell division, their quantification is actually considered as a very valuable tool to estimate thymic function. The most appropriate TREC is deltaRec-Psi(J)alpha TREC or signal joint TREC resulting from deltaRec-Psi(J)alpha rearrangement (TCRD deletion) that occurs late during thymopoiesis, before V(alpha)-J(alpha) rearrangement. Here we describe how TREC quantification is a powerful and reliable method to evaluate the impact of hormones and endocrine disorders upon thymic function [less ▲]

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