Prion diseases are fatal neurodegenerative processes caused by the accumulation of the pathological prion protein, PrPSc. While pathological lesions are limited to the central nervous system (CNS), disease‐specific proteins accumulate and replicate in secondary lymphoid organs prior to neuroinvasion, and their replication there depends on the abundance of cellular prion protein (PrPC). PrPC is expressed in both central and peripheral lymphoid tissues, and up‐ or downregulates innate and adaptive immune responses. In addition to prion diseases, PrPC is also immunologically involved in other neurological disorders and infectious diseases, including Alzheimer's disease and human immunodeficiency virus infection. Herein, we summarize the expression and functions of PrPC in various immunocytes, as well as its immunological and pathological roles in neurodegeneration and infection.

Genetic Creutzfeldt-Jakob disease (gCJD) accounts for approximately 10–15% of human prion diseases. It is an autosomal dominant disease caused by missense or insertion mutations of the gene that encodes prion protein (PRNP). In general, the manifestations and neuropathological changes of gCJD are similar to those of sporadic CJD (sCJD), and the diagnostic sensitivities of cerebrospinal fluid (CSF) markers, electroencephalography (EEG), and magnetic resonance imaging (MRI) are generally lower in gCJD than sCJD. Here we report on a 56-year-old Chinese woman who was diagnosed with gCJD and suspected to have thyroid cancer. The patient carried the glutamate to alanine substitution at codon 196 (E196A) of PRNP, which is quite a rare mutation and has only been reported in China. To our knowledge, this is the fourth case of E196A gCJD in the world. Here, we compared the manifestations and assistant examinations of the current patient with those of three previously reported Chinese patients with E196A gCJD in order to illustrate the common features of E196A gCJD.

Objective Cellular prion protein (PrPC), the primary form of prion diseases pathogen, has received increasing attention for its protective effect against ischaemic stroke. Little is known about its role in peripheral immune responses after cerebral ischaemia/reperfusion (I/R) injury. This study is to detect the variation of splenic CD4+ T lymphocytes differentiation and the concentration of inflammatory cytokines after murine cerebral I/R injury in the context of PRNP expression as well as its influence on the ischaemic neuronal apoptosis. Methods We established the cerebral ischaemic murine model of different PRNP genotypes. We detected the percentage of splenic CD4+PrPC+ T cells of PRNP wild‐type mice and the ratio of splenic Th1/2/17 lymphocytes of mice of different PRNP expression. The relevant inflammatory cytokines were then measured. Oxygen glucose deprivation/reperfusion (OGD/R) HT22 mouse hippocampal neurons were co‐cultured with the T‐cell‐conditioned medium harvested from the spleen of modelled mice and then the neuronal apoptosis was detected. Results CD4+ PrPC+ T lymphocytes in wild‐type mice elevated after MCAO/R. PRNP expression deficiency led to an elevation of Th1/17 phenotypes and the promotion of pro‐inflammatory cytokines, while PRNP overexpression led to the elevation of Th2 phenotype and upregulation of anti‐inflammatory cytokines. In addition, PrPC‐overexpressed CD4+T cells weakened the apoptosis of OGD/R HT‐22 murine hippocampal neurons caused by MCAO/R CD4+ T‐cell‐conditioned medium, while PrPC deficiency enhanced apoptosis. Interpretation PrPC works as a neuron protector in the CNS when I/R injury occurs and affects the peripheral immune responses and defends against stroke‐induced neuronal apoptosis.

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