RESUMEN
The isocortical layer I of human fetal brains obtained from different cases of chromosomal abnormalities (trisomy 18, 21, 22) and controls without pathological disturbances were investigated histologically and immunohistochemically by using the antibodies SMI 311, SMI 35 and SMI 81 (SNAP 25) as well as antibodies against GAP 43 and calretinin. In cases of trisomy 22 the Cajal-Retzius cells in Nissl-sections and in SMI 311-immunopreparations do not reveal any alterations regarding their location or morphology. However, the axonal plexus, selectively labelled with SMI 35, normally located in layer Ib, is malpositioned in Ia. Likewise, SNAP 25- and GAP 43-immunoreactive structures, which were taken as signs of synaptogenesis, are displaced and appear in Ia instead of Ib. Cases of trisomy 18 and 21 show no changes within the organization of layer I. In trisomy 22 the isocortical layer I reveals malpositioned axonal plexus and a corresponding displacement of synaptic proteins. The possible significance of this alteration in the developmental process of the isocortex is discussed.
Asunto(s)
Encéfalo/embriología , Aberraciones Cromosómicas/patología , Cromosomas Humanos Par 22 , Proteínas del Tejido Nervioso/análisis , Trisomía , Encéfalo/patología , Calbindina 2 , Aberraciones Cromosómicas/embriología , Aberraciones Cromosómicas/genética , Trastornos de los Cromosomas , Cromosomas Humanos Par 18 , Cromosomas Humanos Par 21 , Síndrome de Down/genética , Feto , Proteína GAP-43/análisis , Humanos , Proteína G de Unión al Calcio S100/análisisRESUMEN
In vitro studies have demonstrated that intestinal intraepithelial lymphocytes (IEL) are constitutively cytotoxic; however, the mechanism and target of their cytotoxicity are unknown. Apoptosis of intestinal epithelial cells (IEC) and an increase in IEL numbers are classical signs of intestinal graft-versus-host disease (GVHD), although whether IEL can mediate IEC apoptosis directly in GVHD is unclear. Recent evidence suggests that target epithelial organ injury observed in GVHD is predominantly Fas-mediated; therefore, we investigated the possibility that IEL induce apoptosis of IEC through a Fas-mediated mechanism. Here, we demonstrate that the IEL isolated from normal mice readily display potent Fas ligand (FasL)-mediated killing activity after CD3 stimulation, and that IEC express Fas, suggesting that IEC are potential targets for FasL-mediated killing by IEL. In vitro, IEL isolated from GVHD mice have markedly increased FasL-mediated killing potential and are spontaneously cytolytic toward host-derived tumor cells predominantly through a Fas-mediated pathway. In vivo transfer of IEL isolated from GVHD mice induced significantly more IEC apoptosis in F1 wild-type mice than in Fas-defective F1lpr mice. Thus, these results demonstrate that FasL-mediated death of IEC by IEL is a major mechanism of IEC apoptosis seen in GVHD.
