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 ▲]

Neurotrophic Factors: Past and Future

in Acta Neurologica Belgica (1996), 96(3), 203-18

Surface modification of biomaterials in order to control cell adhesion.

Conference (1996)

Preparation of a Macroporous Biodegradable Polylactide Implant for Neuronal Transplantation

in Journal of Biomedical Materials Research (1995), 29(11), 1349-62

This article reports the production of a surgical implant meeting several specific requirements such as biocompatibility, biodegradability, macroporosity, and flexibility. Porosity was controlled by an ... [more ▼]

This article reports the production of a surgical implant meeting several specific requirements such as biocompatibility, biodegradability, macroporosity, and flexibility. Porosity was controlled by an original method consisting of the aggregation of calibrated poly-D,L-lactide microparticles. The size of the interstices between the aggregated microspheres was in a direct relationship to the microsphere diameter. A first approach was based on coating the microspheres with poly(vinyl alcohol) followed by chemically crosslinking the coating layers that were in mutual contact. This method was disregarded because of the acute cytotoxicity of glutaraldehyde used as the crosslinking agent, the absence of macroporosity, and the complete lack of flexibility. A physical technique of aggregation was then tested, which relied on the plasticization of poly-D,L-lactide microspheres with triethylcitrate to the point where microspheres strongly adhered to each other when they were in contact. This method has proved to be straightforward and definitely superior to the chemical approach, particularly with respect to cytotoxicity, control of macroporosity, and flexibility. A polymer support was thus successfully which was biodegradable, macroporous( interconnected pores of 10-100 microns in diameter), and flexible. This potential medical device is presently being used for neuronal transplantation in the central nervous system. [less ▲]

Transplants of syngenic cultured, DRG-derived Schwann cells into the injured adult rat spinal cord.

Conference (1993, June 18)

Retinoic Acid Stimulates Regeneration of Mammalian Auditory Hair Cells

in Science (1993), 260(5108), 692-5

Sensorineural hearing loss resulting from the loss of auditory hair cells is thought to be irreversible in mammals. This study provides evidence that retinoic acid can stimulate the regeneration in vitro ... [more ▼]

Sensorineural hearing loss resulting from the loss of auditory hair cells is thought to be irreversible in mammals. This study provides evidence that retinoic acid can stimulate the regeneration in vitro of mammalian auditory hair cells in ototoxic-poisoned organ of Corti explants in the rat. In contrast, treatment with retinoic acid does not stimulate the formation of extra hair cells in control cultures of Corti's organ. Retinoic acid-stimulated hair cell regeneration can be blocked by cytosine arabinoside, which suggests that a period of mitosis is required for the regeneration of auditory hair cells in this system. These results provide hope for a recovery of hearing function in mammals after auditory hair cell damage. [less ▲]

In Vitro and in Vivo Modulation of 5-Hydroxytryptamine-, Thyrotropin-Releasing Hormone- and Calcitonin-Gene Related Peptide-Like Immunoreactivities in Adult Rat Sensory Neurons

in Neuroscience (1992), 51(2), 401-10

In a previous work we have shown that culturing adult rat dorsal root ganglia neurons modifies their neurotransmitter phenotype in such a way that cultured neurons synthesize transmitters that are not ... [more ▼]

In a previous work we have shown that culturing adult rat dorsal root ganglia neurons modifies their neurotransmitter phenotype in such a way that cultured neurons synthesize transmitters that are not found in situ, while several other transmitters are expressed in a much higher percentage of neurons in culture than in situ [Schoenen J. et al. (1989) J. Neurosci. Res. 22, 473-487]. The aim of the present study was to investigate the origin and the nature of the relevant environmental signals that allow this plasticity to be expressed, focusing on three neurotransmitters: 5-hydroxytryptamine, thyrotropin-releasing hormone and calcitonin-gene related peptide. The main results can be summarized as follows: (1) culturing cells in fetal calf serum or on feeder layers of astrocytes, Schwann cells or fibroblasts partially inhibits the serotoninergic phenotype of dorsal root ganglia neurons; (2) in vivo disconnection of dorsal root ganglia from their spinal targets but not from their peripheral or supraspinal targets induces a significant increase of the percentage of 5-hydroxytryptamine- and thyrotropin-releasing hormone-positive neurons in disconnected ganglia; (3) growth factors such as ciliary neuronotrophic factor or basic fibroblast growth factor but not nerve growth factor repress 5-hydroxytryptamine and calcitonin gene-related peptide immunoreactivity in cultured sensory neurons. In conclusion, neurotransmitter gene expression of adult dorsal root ganglia neurons is controlled by complex influences. Our data suggest that thyrotropin-releasing hormone and 5-hydroxytryptamine gene expression are tonically repressed in vivo by factors originating from the spinal segmental level and that growth factors such as ciliary neurotrophic factor or basic fibroblast growth factor could be potential vectors of this repressing effect. [less ▲]