Contributions to our understanding of T cell physiology through unveiling the T cell proteome

Since the sequencing of the human genome was completed, attention has turned to examining the functionality of the molecular machinery, in particular of protein expression. Differential proteome analysis by two-dimensional electrophoresis has been adopted to study changes in T cell proteomes during T cell activation, and this work is increasing our understanding of the complexity of signals elicited across multiple pathways. The purpose of this review is to summarize the available evidence in the application of proteomic techniques and methodologies to understand T cell receptor activation from lipid raft and cytoskeletal rearrangements, through to signalling cascades, transcription factor modulation and changes in protein expression patterns. These include post-translational modifications, which are not encoded by the genome. © 2007 British Society for Immunology.

Relationship between the microcirculation and the pathological changes in the spradic and variant forms of Creutzfeldt-Jakob Disease (CJD)

This chapter is concerned with the influence of the brain microcirculation on the development of the pathological changes in Creutzfeldt-Jakob disease (CJD). Hence, the spatial correlations between the vacuolation, prion protein (PrP) deposits, and the blood vessel profiles were studied in immunolabelled sections of the cerebral cortex, hippocampus, and cerebellum in two subtypes of CJD, viz., sporadic Creutzfeldt-Jakob disease (sCJD) and variant CJD (vCJD). In sCJD, both the vacuolation and the ‘synaptic-type’ PrP deposits were spatially correlated with the blood vessels; the PrP deposits being the more strongly correlated than the vacuoles. In vCJD, there were no significant spatial correlations between either the vacuolation or the diffuse-type of PrP deposit and the microvessels. By contrast, a consistent pattern of spatial correlation was observed in gyri of the cerebral cortex between the florid PrP deposits and blood vessels. In both sCJD and vCJD, the frequency of positive spatial correlations was similar in the different gyri of the cerebral cortex and in the upper compared with the lower laminae. In conclusion, the microcirculation appears to be more significantly involved in determining the pathological changes in sCJD than in vCJD. The spatial correlations of the florid PrP deposits in vCJD and the synaptic deposits in sCJD and the blood vessels may be attributable to factors associated with the microcirculation which enhance the aggregation of PrP molecules rather than representing a possible haematogenous spread of the disease.

Pathological changes in the primary visual cortex (Area V1) in Creutzfeldt-Jakob syndrome

About 10% of patients with Creutzfeldt-Jakob syndrome (disease) (CJD) exhibit visual symptoms at presentation and approximately 50% during the course of the disease. The objectives of the present study were to determine, in two subtypes of CJD, viz., sporadic CJD (sCJD) and variant CJD (vCJD), the degree of pathological change in the primary visual cortex (area V1) and the extent to which pathology in V1 may influence visual function. The vacuolation (‘spongiform change’), surviving neurons, glial cell nuclei, and deposits of prion protein (PrP) were quantified in V1 obtained post-mortem in nine cases of sCJD and eleven cases of vCJD. In sCJD, the vacuoles and PrP deposits were regularly distributed along the cortex parallel to the pia mater in clusters with a mean dimension from 450 to 1000 µm. Across the cortex, the vacuolation was most severe in laminae II/III and the glial cell reaction in laminae V/VI. Surviving neurons were most abundant in laminae II/III while PrP deposition either affected all laminae equally or was maximal in lamina II/III. In vCJD, the vacuoles and diffuse PrP deposits were distributed relatively uniformly parallel to the pia mater while the florid deposits were consistently distributed in regular clusters. Across V1, the vacuoles either exhibited a bimodal distribution or were uniformly distributed. The diffuse PrP deposits occurred most frequently in laminae II/III while the florid deposits were more generally distributed. The data suggest that in both sCJD and vCJD, pathological changes in area V1 may affect the processing of visual information in laminae II/III and its transmission from V1 to V2 and to subcortical visual areas. In addition, the data suggest an association in sCJD between the developing pathology and the functional domains of V1 while in vCJD the pathology is more uniformly distributed. These changes could be a factor in the development of poor visual acuity, visual field defects, cortical blindness, diplopia, and vertical gaze palsy that have been observed in Creutzfeldt-Jakob syndrome.