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

Abstract

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.

Persistent Infection of Human Thymic Epithelial Cells by Coxsackievirus B4

“…Our data confirm previous observations that TEC spontaneously produce cytokines in vitro (18,21) and that viruses can modulate the production of cytokines by TEC, without a virusinduced cytopathic effect (31). However, our study is different from those of other investigators, because we report a significantly increased production of IL-6, LIF, and GM-CSF by TEC in response to CVB4 and because CVB4 replication was investigated at the molecular level.…”

Ontogenesis and functional aspects of oxytocin and vasopressin gene expression in the thymus network

“…The cell feature, morphology, and overall distribution correspond to TEC. This is in accordance with our previous immunocytochemical studies showing that OT and VP are identified in human and murine TEC, including thymic nurse cells (TNC) (Geenen et al, 1988;Martens et al, 1996b;Robert et al, 1991). OT and VP transcription in the thymus is therefore coupled to mRNA translation and precursor processing.…”

“…As a source of hypothalamus-specific antigens, OT and VP are also expressed in TEC from different species, although with a dominance of OT at the peptide level. Thymic OT is not secreted but targeted to the outer surface of TEC plasma membrane where it is recognized by specific monoclonal antibodies (mAbs) (Martens et al, 1996b). Specific and functional receptors for these peptides are expressed by human thymocytes and a murine double negative (DN) CD4…”

Coxsackievirus B4 infection of murine foetal thymus organ cultures

“…Self-tolerance is initiated in the thymus during T-cell ontogeny [Geenen and Kroemer, 1993;Martens et al, 1996;Geenen et al, 2001], a multi-step process which starts as soon as foetal life. The thymus fulfils this function by two complementary mechanisms: the deletion of T cells directed against self-antigens presented in the thymic cellular environment (thymic epithelial cells, macrophages and dendritic cells) by major histocompatiblity complex (MHC) proteins, and the generation of self-antigen specific regulatory T cells (T REG ).…”