Vitamin C, one of essential micronutrients, has been reported to modulate the humoral immune responses in some mammals. We investigated whether vitamin C might modulate this response in mice by directly affecting B cells. Splenic B cells were isolated and activated by CD40- and B cell receptor-ligation in vitro. The cells were cultured with a pretreatment of vitamin C from 0 to 1 mM of concentrations. Vitamin C slightly increased apoptosis of B cells dose-dependently and behaved as an antioxidant. We found that in vivo administration of vitamin C by intraperitoneal injection affected isotype switching as previously reported: the titer of antigen-specific IgG1 antibody was decreased, while that of IgG2a was unaffected. Somewhat different from those observed in vivo, in vitro exposure to vitamin C slightly decreased isotype switching to IgG1 and increased isotype switching to IgG2a. Pretreatment with vitamin C in the safe range did not affect either proliferation of cultured B cells or the expression of CD80 and CD86 in those cells. Taken together, in vivo results suggest that vitamin C acts to modulate isotype switching in the mouse. However, because of our in vitro results, we suggest that the modulation exerted by vitamin C in vivo is by indirectly affecting B cells, perhaps by directly influencing other immune cells such as dendritic cells.
T cells play a pivotal role in the initiation and progression of multiple sclerosis. We have found that 1,4-aryl-2-mercaptoimidazole (KRM-III) inhibited T-cell antigen receptor-and phorbol myristate acetate/ionomycin-induced activation of nuclear factor of activated T cells (NFAT) and T-cell proliferation with an IC 50 of 5 M. The KRM-III-mediated inhibitory effect was specific for NFAT activation but not for nuclear factor B. Oral administration of 90 mg/kg KRM-III resulted in complete abrogation of anti-CD3 antibody-induced T-cell activation and a 45.8% reduction in footpad swelling in bovine serum albumininduced delayed-type hypersensitivity. In the murine experimental autoimmune encephalomyelitis (EAE) model, oral administration of KRM-III significantly attenuated the severity of disease when given before or after disease onset. Draining lymph node cells from KRM-III-treated mice showed markedly reduced proliferation in response to myelin oligodendrocyte glycoprotein peptide. Histological analysis indicated that KRM-III reduced the infiltration of inflammatory cells to the white matter of spinal lumbar cords. These results demonstrate that KRM-III efficiently inhibits T-cell activation and inflammatory responses and lessens EAE clinical signs, which suggest KRM-III as a potential lead compound for the treatment of T-celldriven autoimmune diseases.Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system, which is characterized by inflammatory lesions consisting of T cells, B cells, and macrophages in the white matter of the central nervous system (Raine, 1984). Although the etiology is not well known, MS has been considered as a CD4 T cell-dependent disease (Steinman, 2001;Hafler, 2004). This notion is based on the genetic linkage of MS susceptibility with major histocompatibility complex II genes (Zamvil and Steinman, 1990) and the high frequency of activated, myelin-reactive T cells in the periphery as well as cerebrospinal fluid of MS patients (Traugott et al., 1983;Hauser et al., 1986). An early study demonstrated that transgenic mice expressing myelin-specific T-cell antigen receptor (TCR) spontaneously developed demyelinating disease, suggesting that myelin-specific T cells might be one of the causative agents of MS and can initiate the inflammatory disease process (Goverman et al., 1993). Moreover, the experimental autoimmune encephalomyelitis (EAE) model, an animal model of human MS, was
This paper introduces an adaptive yaw control scheme based on the estimation of the vehicle mass, yaw inertia and center of gravity (CG) position. The control deigns for three-axle road vehicles, which can be trucks, buses, or even three-axle passenger cars. System parameters of these vehicles vary significantly due to varying conditions, such as unloading and fully-loading of payloads. As a result, control references and fixed-model-based controller lose efficacy. The proposed adaptive yaw control compensates these issues, utilizing the integration of a least-square based parameter identification algorithm and a Model Reference Adaptive Control (MRAC) law. Simulation test results verify the effectiveness of the proposed adaptive control scheme.
Background: Based on outstanding progresses in animal experiments, vaccines for some human tumors have been developed. However, clinical effects of these vaccines have been far below than expected. This discrepancy might come from differences between animal models and human patients with respect to immunocompetency. The immune status of mice after tumor inoculation has not been well studied, which make us cautious in interpreting and applying the results from mice to human. We evaluated cell-mediated immune responses in mice after tumor cell inoculation. Methods: Mice were inoculated with TA3Ha, CT26, or 4T1. Delayed-type hypersensitivity (DTH) responses were induced 2-4 weeks after inoculation using 2,4-dinitro-1-fluorobenzene as an antigen. The relationships between the severity of DTH responses and the duration of tumor inoculation or the size of tumor mass were analyzed. Results: In TA3Ha groups, DTH response was elevated 2 weeks after inoculation, but depressed after 4 weeks, compared to the control group. When analyzed based on the sizes of tumor masses elicited, DTH responses were inversely related to the mass size, especially in those greater than 10 mm in diameter. In CT26 groups, while the duration after inoculation did not affect the severity of DTH responses, those with large mass showed depressed responses regardless the duration of inoculation. 4T1 cells grew so slowly that the size of tumor mass was small even 4 weeks after inoculation, and this group showed much higher DTH responses compared to that of tumor-free group. Conclusion: At least in an experimental setting where tumor model was induced by inoculating tumor cell lines into immunologically competent mice, the host immune response was elevated in early stage, and then depressed in late stage when the mass grew over a critical size.
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