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We recently demonstrated that newly developed non-viral amyloid-β (Aβ) DNA vaccines are safe and effective in reducing Aβ burdens in the brains of Alzheimer's disease (AD) model mice. The present study was undertaken to examine whether DNA vaccines effectively and safely reduce Aβ deposition in the brain of rhesus monkeys. For this purpose, DNA vaccines or empty vector at a dose of 3 mg were injected intramuscularly on a biweekly basis into rhesus monkeys (15--18 years old). Before and during vaccination, blood was drawn once a month and used for hematological and biochemical examinations. Six months after the first vaccination, it was demonstrated that anti-Aβ antibodies in plasma of vaccinated monkeys were significantly elevated than that of control monkeys. Immunohistochemical examinations revealed that DNA vaccination reduced the Aβ burden to approximately 50% of that found in control monkeys (p=0.026). There was neither inflammation nor microhemorrhage in the brain and no significant changes in cytokine and chemokine levels in the blood throughout the observation period. Taken together, DNA vaccination to monkeys is safe and effective in Aβ reduction and provides useful information for performing preclinical and clinical trials. [ABSTRACT FROM AUTHOR]

Background: Olig1 is a basic helix-loop-helix (bHLH) transcription factor that is essential for oligodendrogenesis and efficient remyelination. However, its role in neurodegenerative disorders has not been well-elucidated. Methodology/Principal Findings: Here we investigated the effects of Olig1 deficiency on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We show that the mean disease onset of myelin oligodendrocyte glycoprotein (MOG)-induced EAE in Olig1-/- mice is significantly slower than wide-type (WT) mice (19.8±2.2 in Olig1-/- mice and 9.5±0.3 days in WT mice). In addition, 10% of Olig1-/- mice did not develop EAE by the end of the observation periods (60 days). The severity of EAE, the extent of demyelination, and the activation of microglial cells and astrocytes in spinal cords, were significantly milder in Olig1-/- mice compared with WT mice in the early stage. Moreover, the visual function, as assessed by the second-kernel of multifocal electroretinograms, was better preserved, and the number of degenerating axons in the optic nerve was significantly reduced in Olig1-/- mice. Interestingly, Olig1 deficiency had no effect on T cell response capability, however, it reduced the expression of myelin proteins such as MOG, myelin basic protein (MBP) and myelin-associated glycoprotein (MAG). The expression of Olig2 remained unchanged in the optic nerve and brain, and it was reduced in the spinal cord of Olig1-/- mice. Conclusions/Significance: Our results suggest that the Olig1 signaling pathways may be involved in the incidence rate and the severity of neurological symptoms in MS. [ABSTRACT FROM AUTHOR]

Abstract: Increasing evidence strongly suggest that CD4+CD25+ regulatory T (Treg) cells play a pivotal role in suppressing the development of autoimmune diseases. However, it remains poorly understood how these cells are involved in the persistence of, or recovery from, the diseases. In the present study, we examined the role of CD4+CD25+ Treg cells in chronic EAE and compared the results with those obtained in acute EAE. In EAE lesions, CD25+ cells decreased rapidly at the beginning of chronic EAE, whereas these cells were maintained at high levels during the recovery from acute EAE. The number of Foxp3+CD4+CD25+ Treg and levels of Foxp3 mRNA in the lymphoid organ were significantly lower in chronic EAE. Importantly, the regulatory function of individual CD4+CD25+ Treg cells was maintained in animals with chronic EAE. Furthermore, adoptive transfer of activated CD4+CD25+ Treg cells suppressed the development of chronic EAE. These findings suggest that impairment of the CD4+CD25+ Treg response is critical for development of chronic autoimmune diseases, and can be adjustable by autologous Treg transplantation. [Copyright &y& Elsevier]

Infection with Shiga toxin (Stx)-producing Escherichia coli (STEC) causes hemorrhagic colitis and hemolytic uremic syndrome. TMA-15 is a humanized monoclonal antibody against Stx2, a major pathogenic factor. In a mouse infection model that used B2F1, a virulent STEC strain, the efficacy of TMA-15 was assessed when it was administered after bacterial and toxin exposure. In this model, a time-course analysis of the serum Stx2 level showed that the toxin was detectable from 24 h after infection. In an evaluation of the time-dependent efficacy, treatment with TMA-15 up to 24 h after infection ameliorated the lethal challenge, although treatment at 48 h showed no efficacy. To determine the effective dose, escalating doses were administered at 24 h after infection. The number of mice that survived after doses of 0, 0.25, 0.5, 1.0, and 2.0 mg/kg were 0⁄20, 11⁄20, 17⁄20, 20⁄20, and 20⁄20, respectively. These findings suggest that TMA-15 shows potential for prevention of severe complications associated with STEC infection. [ABSTRACT FROM AUTHOR]

In order to quantify encephalitogenic effector T cells in the subarachnoid space (SAS) and spinal cord afflicted with experimental autoimmune encephalomyelitis (EAE), we immunized Lewis rats using myelin basic protein and complete Freund's adjuvants and analyzed the inflammatory cells by fluorescence-activated cell sorter (FACS) and immunohistochemistry. At the induction stage of EAE, the majority of observed inflammatory cells were determined by immunohistochemistry to be either CD4+ T cells or OX42+ macrophages. Among CD4+ T cells, both CD45R high (OX22+) and CD45R low (OX22-) T cells were found in the SAS, while in the neighboring subpial spinal cord parenchyma, CD45R low (OX22-negative)/CD4+ T cells predominated. FACS analysis showed that CD45RC low/CD4+ T cells was 83% of total CD4+ T cells in the SAS, while 94% of cells with the same phenotype were found in the parenchyma of rat spinal cords afflicted with EAE. This finding suggests that during the induction stage of EAE, effector T cells preferentially migrate into the subpial parenchyma from the SAS. Thereafter, suppressor T cells follow, which may lead to the spontaneous recovery from EAE paralysis. [ABSTRACT FROM AUTHOR]

Hybridomas producing human monoclonal antibodies (MAbs) against herpes simplex virus (HSV) were established by fusing human tonsillar lymphocytes with mouse myeloma cells. Three hybridomas have been stably producing MAbs for >16 months. All three MAbs — H1, H2, and H3 — were of the IgGl isotype and recognized the gB glycoprotein of HSV types 1 and 2 (HSV-1 and HSV-2). MAbs H2 and H3 not only bound to the surface membrane of HSV-infected cells but also neutralized both HSV-1 and HSV-2, whereas MAb HI had neither activity. In mouse infection experiments, MAbs H2 and H3 showed a potent protective effect against HSV-1 infection, whereas MAB H1 was less protective. Furthermore, the development of zosteriform skin lesions in athymic nude mice was suppressed by administering MAb H2. These results suggest that human MAbs might provide passive immunization against HSV infections in humans. [ABSTRACT FROM PUBLISHER]