Characterization of the Insulin-Like Growth Factor Axis in the Human Thymus

in Journal of Neuroendocrinology (1999), 11(6), 435-40

The components of the insulin-like growth factor (IGF) axis have been investigated in the normal human thymus. Using ribonuclease protection assays (RPA), IGF-II transcripts were detected in the normal ... [more ▼]

The components of the insulin-like growth factor (IGF) axis have been investigated in the normal human thymus. Using ribonuclease protection assays (RPA), IGF-II transcripts were detected in the normal human thymus. By reverse transcriptase polymerase chain reaction (RT-PCR) analyses, promoters P3 and P4 were found to be active in the transcription of IGF2 gene within human thymic epithelial cells (TEC). No IGF-II mRNA could be detected in human lymphoid Jurkat T cells with 30 cycles of RT-PCR. By Northern blot analyses, IGFBP-2 to -6 (but not IGFBP-1) were found to be expressed in TEC with a predominance of IGFBP-4. Interestingly, Jurkat T cells only express IGFBP-2 but at high levels. The type 1 IGF receptor was detected in Jurkat T cells but not in human TEC. The identification of the components of the IGF axis within separate compartments of the human thymus adds further evidence for a role of this axis in the control of T-cell development. The precise influence of thymic IGF axis upon T-cell differentiation and immunological self-tolerance however needs to be further investigated. [less ▲]

Molecular dissection of the insulin-like growth factor axis in the human thymus

in Diabetologia (1997), 40

Developmental and evolutionary aspects of thymic T-cell education to neuroendocrine self

in Acta Haematologica (1996), 95

Cellular and molecular mechanisms involved in thymic T-cell education to neuroendocrine self principles

in International Journal of Thymology (1996), 4

Cryptocrine Signaling in the Thymus Network and T Cell Education to Neuroendocrine Self-Antigens

in Journal of Molecular Medicine : Official Organ of the 'Gesellschaft Deutscher Naturforscher und Ärzte' (1995), 73(9), 449-55

Both during phylogeny and ontogeny the thymus appears as a nodal point between the two major systems of cell-to-cell signaling, the neuroendocrine and immune systems. This review presents the experimental ... [more ▼]

Both during phylogeny and ontogeny the thymus appears as a nodal point between the two major systems of cell-to-cell signaling, the neuroendocrine and immune systems. This review presents the experimental observations which support a dual role in T cell selection played by the thymic repertoire of neuroendocrine polypeptide precursors. Through the mode of cryptocrine intercellular signaling thymic neuroendocrine-related precursors synthesized in thymic epithelial cells have been shown to influence the early steps in T cell differentiation. In addition, thymic neuroendocrine-related polypeptides are a source of self-antigens which are presented by the major histocompatibility system of the thymic epithelium. Preliminary data also suggest that the intrathymic T cell education to neuroendocrine self-antigens is not strictly superimposible to the antigen presentation by dedicated presenting cells. Insulin-like growth factor-II (IGF-II) was identified as one dominant member of the insulin family expressed by thymic epithelial and nurse cells. The intrathymic presentation of IGF-II or IGF-II derived self-antigens is under current investigation. If further confirmed, the central tolerogenic properties of IGF-II could be considered in the elaboration of a strategy for an efficient and safe prevention of insulin-dependent diabetes. [less ▲]

Evidence that insulin-like growth factor 2 (IGF2) is the dominant thymic peptide of the insulin superfamily

in The Endocrine Society (Ed.) Proceedings of the 75th Annual Meeting of the Endocrine Society (1993)

La communication cryptocrine et la reconnaissance des fonctions neuroendocrines par les cellules T au cours de leur différenciation

in Revue Française d'Endocrinologie Clinique, Nutrition, et Métabolisme (La) (1992), 33

Le thymus, organe lymphoïde primaire responsable du développement des lymphocytes T, est le site d'expression de différents peptides appartenant à des familles hormonales distinctes. Le modèle classique ... [more ▼]

Le thymus, organe lymphoïde primaire responsable du développement des lymphocytes T, est le site d'expression de différents peptides appartenant à des familles hormonales distinctes. Le modèle classique de la neurosécrétion établi pour l'axe hypothalamo-neurohypophysaire ne peut cependant s'appliquer à la sécrétion de tels signaux par les cellules épithéliales thymiques. Un nouveau modèle de communication cellulaire, celui de la communication cryptocrine, a été proposé par John W. Funder pour décrire les échanges d'information entre une cellule épithéliale fixe et des cellules mobiles en différenciation à leur contact. Dans le thymus, la communication cryptocrine est étroitement associée à la présentation de la structure moléculaire du Soi par les molécules d'histocompatibilité (CMH) aux lymphocytes T au cours de leur différenciation. Sur la base de nos observations, le modèle du répertoire thymique des autoantigènes neuroendocrines permet de transposer au niveau moléculaire le double rôle physiologique du thymus dans les phénomènes de sélections négative et positive des cellules T, et d'apporter un éclairage nouveau sur les mécanismes responsables de la tolérance immunitaire centrale aux fonctions neuroendocrines. [less ▲]