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 ▲]

Thymic insulin-related polypeptides in diabetes-prone Bio-Breeding rats

in Diabetologia (1999), 42 (Suppl. 1)

De nouveaux acteurs dans la physiopathologie du metabolisme de l'eau: les aquaporines

in Revue Médicale de Liège (1999), 54(11), 867-74

Aquaporins are transmembrane proteins mediating water transport across plasma membrane of animal, vegetal or bacterial cells. Among the ten aquaporins known in mammals, six are located in kidney and take ... [more ▼]

Aquaporins are transmembrane proteins mediating water transport across plasma membrane of animal, vegetal or bacterial cells. Among the ten aquaporins known in mammals, six are located in kidney and take part in urine concentration. AQP2 is vasopressin regulated, it is the only family member to be implicated in human pathology, such as nephrogenic diabetes insipidus, congestive heart failure, hepatic cirrhosis, nephrotic syndrome or SIADH. Aquaporins are expressed in a wide variety of tissues, such as brain or gastrointestinal tractus, and suggest a role in water tissue exchange, but their real function is still not define. To know the physiological impact of aquaporins, AQP1, AQP3, AQP4 and AQP5 knockout mice have been created and their phenotype analysed. [less ▲]

Neurohypophysial Peptides Stimulate the Phosphorylation of Pre-T Cell Focal Adhesion Kinases

in Neuroendocrinology (1998), 67(4), 282-9

Thymic oxytocin (OT) behaves as a cryptocrine signal targeted at the outer surface of thymic epithelial cell plasma membrane from where OT is able to interact with neurohypophysial peptide receptors ... [more ▼]

Thymic oxytocin (OT) behaves as a cryptocrine signal targeted at the outer surface of thymic epithelial cell plasma membrane from where OT is able to interact with neurohypophysial peptide receptors expressed by pre-T cells. Immature T cells bear a receptor of the V1 subtype, while OT receptors are predominantly expressed by cytotoxic CD8+ lymphocytes. In both T cell types, neurohypophysial peptide receptors transduce OT via the phosphoinositide pathway. Protein tyrosine phosphorylation is an early event of T cell activation. Western blots of murine pre-T cells (RL12-NP line) proteins probed with anti-phosphotyrosine (PY-20) revealed a great number of proteins the phosphorylation of which increased either with OT or vasopressin treatment. Two were immunoprecipitated with anti-focal adhesion kinase (FAK) mAb 2A7 and were identified one as p125FAK and the other as a coprecipitating 130-kDa protein. The p125FAK is connected to the Ras/MAPK pathway and is also implicated in TCR/CD3 signalling in T cell. Another protein phosphorylated by OT in RL12-NP was identified as paxillin, a 68-kDa protein localised at focal adhesion sites and associated with p 125FAK. These results indicate that phosphorylation of focal adhesion kinase may be induced in pre-T cell by thymic OT. [less ▲]

Neurohypophysial peptides stimulate the phosphorylation of pre-T cell focal adhesion kinases

in Neuroendocrinology (1998), 67

Thymic expression of neuroendocrine self-peptide precursors: role in T-cell survival and self-tolerance

in Journal of Neuroendocrinology (1998), 10

Phosphorylation of Proteins Induced in a Murine Pre-T Cell Line by Neurohypophysial Peptides

in Advances in Experimental Medicine and Biology (1998), 449

Identification of neurotensin-related peptides in human thymic epithelial cell membranes and relationship with MHC class I molecules

in Journal of Neuroimmunology (1997), 76

This study shows the expression at the cell surface of human thymic epithelial cells (TEC) of a neurotensin (NT)-like immunoreactivity. NT radio-immunoassay (RIA) revealed that cultured human TEC contain ... [more ▼]

This study shows the expression at the cell surface of human thymic epithelial cells (TEC) of a neurotensin (NT)-like immunoreactivity. NT radio-immunoassay (RIA) revealed that cultured human TEC contain ± 5 ng immunoreactive (ir) NT/106 cells, of which 5% is associated with plasma cell membranes. HPLC analysis of NT-ir present in human TEC showed a major peak of NT-ir corresponding to NT1–13. NT-ir was not detected in the supernatant of human TEC cultures. Using an affinity column prepared with a anti-MHC class I monoclonal antibody, NT-ir-related peptides were retained on the column and eluted together with MHC class I-related proteins. According to the elution time on HPLC of these peptides, they correspond to intact NT1–13, as well as to smaller fragments of NT1–13. [less ▲]

Cytokine Production by Human Thymic Epithelial Cells: Control by the Immune Recognition of the Neurohypophysial Self-Antigen

in Regulatory Peptides (1996), 67(1), 39-45

Oxytocin (OT) has been shown to be the dominant peptide of the neurohypophysial family expressed by thymic epithelial and nurse cells (TEC/TNC) in various species. Thymic OT is not secreted but, after ... [more ▼]

Oxytocin (OT) has been shown to be the dominant peptide of the neurohypophysial family expressed by thymic epithelial and nurse cells (TEC/TNC) in various species. Thymic OT is not secreted but, after translocation of a hybrid neurophysin/MHC class I protein, is integrated within the plasma membrane of 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 mAbs to OT on cytokine productions by cultures enriched in human TEC. 75-85% pure TEC cultures were prepared from human thymic fragments. Using immunofluorescence and confocal microscopy, ir-OT, ir-interleukin-1 beta (IL-1 beta), 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-1 beta) were detected in the supernatants 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 neurohypophysial family. [less ▲]

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

in Acta Haematologica (1996), 95