Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we have compared the T cell antigenic determinants on nucleoprotein (NP) of influenza A/NT/60/68 virus recognized by BALB/c mice (H-2d) after vaccination using several different vehicles with the determinants recognized after exposure to infectious virus. Mice were immunized s.c. with: 1) purified recombinant NP with three different adjuvants--alum, saponin, or CFA; 2) whole inactivated A/Okuda virus in PBS or saponin; or 3) live attenuated Salmonella typhimurium AroA- vector expressing NP. A series of overlapping synthetic peptides that cover more than 90% of the amino acid sequence of NP were used to map the Th cell epitopes. The results showed that the same limited number of major epitopes were recognized after each of the different immunization regimes. Secondary in vivo boosting using the same vehicles as for the primary immunization did not increase the number of different T cell sites recognized. The T cell responses after intranasal infection with infectious A/NT/60/68 or A/PR/8/34 virus also showed a similar pattern of recognition of the major CD4-positive T cell epitopes. The only exception was that the region corresponding to residues 401-419 was only recognized after exposure to NP from A/NT/60/68 but not A/PR/8/34. This is probably because the two viruses differ in amino acid sequence at positions 408 and 411 within this part of the NP molecule. In contrast to the results observed with CD4-positive T cell epitopes, the major determinant recognized by CD8-positive T cells was only presented after live viral infection. The results in this study have important implications for vaccine design, inasmuch as they indicate that the same dominant CD4 T cell determinants on NP presented by vaccination with NP are also recognized by T cells from mice exposed to infectious virus.
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PMID:Selection of the same major T cell determinants of influenza nucleoprotein after vaccination or exposure to infectious virus. 171 66

Idiotype/anti-idiotype networks have been extensively investigated in such conventional animal models as the mouse and the rabbit. However, systems of veterinary interest have remained largely unexplored. A monoclonal target idiotype, with which to begin such studies in cattle was provided by LHRB 19.17 an interspecific bovine x mouse hybridoma. This hybridoma was constructed by the fusion of supramammary lymph node cells from S. agalactiae-immunized lactating Holsteins with the Ig synthesis-permissive established cell line, SP 2/0. Two collections of monoclonal anti-idiotype antibodies were generated by fusion of spleen cells from LHRB 19.17-immunized Balb/c or A/J mice immunized with the monoclonal bovine idiotype, LHRB 19.17. Many of the anti-idiotypes inhibited binding of LHRB 19.17 to S. agalactiae, but only one, LHRAID 2.71, proved to be an internal image of a S. agalactiae epitope. Immunization of C/D outbred rats by priming with 100-300 micrograms of LHRAID 2.71 emulsified in CFA followed by a 300 micrograms boost at day 32 elicited anti- S. agalactiae antibody in 4/4 animals tested. Similarly, the injection of two lactating Holsteins with the anti-id resulted in the production of anti- S. agalactiae antibody in serum and milk. In both rats and cattle, the administration of the antigen-mimicking anti-idiotype induces the appearance of S. agalactiae-reactive horseradish peroxidase-streptavidin conjugate; LHRBs, interspecific bovine x mouse hybridomas secreting bovine Ig; LHRAID.X, monoclonal anti-bovine idiotype antibodies derived against LHRB 19.17; PBS, phosphate buffered saline; PBS/BSA, PBS containing 0.1% bovine serum albumin: antibody [AB3] that competes with LHRB 19.17 [AB1] for binding to LHRAID 2.71 [AB2]. It should also be noted that the immunization of C/D rats with S. agalactiae does not result in the appearance of idiotypes which compete with LHRB 19.17 for binding to LHRAID 2.71. We have concluded that immunization of two widely divergent species with the antigen mimicking LHRAID 2.71 induced a S. agalactiae-reactive idiotype which was not detectable in the immune response of rats to S. agalactiae.
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PMID:Comparative idiotype network interactions: antigen mimicry by an anti-bovine idiotype monoclonal antibody in rats and cattle. 245 77

To explore the mechanisms responsible for the development of tolerance to allografts after intrathymic (IT) injection of alloantigen, the well-defined model of experimental autoimmune encephalomyelitis (EAE), which mimics the human autoimmune disease multiple sclerosis, was used. This inflammatory neurologic syndrome is initiated by myelin basic protein (MBP)-reactive CD4+ T lymphocytes restricted to self-MHC class II molecules. Naive adult, EAE-susceptible Lewis (RT1(1) rats were treated IT, i.v., or i.p. with a single dose (100 micrograms) of guinea pig-myelin basic protein (GP-MBP 1-176) in PBS plus 1 ml rabbit anti-rat lymphocyte serum i.p. Twenty-one days later, all rats were challenged by intradermal hind footpad injections of 50 micrograms GP-MBP in PBS emulsified in CFA. Only IT, but not i.p. or i.v., administration of GP-MBP plus anti-lymphocyte serum conferred marked resistance to a subsequent systemic challenge of GP-MBP, as demonstrated by the prevention of weight loss and paralysis characteristic of EAE. The IT administration dramatically decreased the size and number of histologic perivascular infiltrates observed per visual field in spinal cord of the tolerant animals and decreased GP-MBP-specific T lymphocyte in vitro proliferation (p < 0.01), whereas proliferation to a nonspecific mitogen (Con A) was not altered. With the addition of rIL-2, the decreased Ag-specific proliferative responses of IT-treated animals increased to control levels. Adoptive transfer of 100 x 10(6) splenocytes from tolerant hosts i.v. to naive syngeneic Lewis rats challenge with 100 micrograms GP-MBP in CFA had no effect on clinical or histologic EAE. Exposure of MBP to maturing thymocytes results in functionally immunounresponsive lymphocytes and prevention of autoimmune EAE.
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PMID:Immunological tolerance to a defined myelin basic protein antigen administered intrathymically. 752 8

The effects of the novel immunosuppressant Deoxyspergualin (DSP) on the development of experimental autoimmune thyroiditis (EAT) in CBA mice were studied. For EAT induction, the mice were immunized with 100 micrograms of porcine thyroglobulin (p Tg) emulsified in CFA on day 0 and in IFA, for boosting, on day 14. Twenty-eight days after primary immunization, histological and serological signs of EAT occurred in control mice treated with PBS which showed marked lymphoid infiltration of the thyroid glands along with increased serum titres of anti-pTg antibodies. Development of both these EAT features was significantly suppressed when the mice were treated with 2.5 mg/kg body weight DSP, given daily, five times a week, from day -2 to day +28 after immunization. The effect appeared to be dose-dependent and DSP was ineffective when given under the same experimental conditions at the dose of 0.5 mg/kg body weight. No DSP-toxic effects could be observed during the experiment. These results provide further evidence for the powerful immunosuppressive properties of DSP and suggest that this drug may be used in the treatment of autoimmune thyroid diseases and other T-cell mediated autoimmune disorders in humans.
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PMID:Protection from experimental autoimmune thyroiditis in CBA mice with the novel immunosuppressant deoxyspergualin. 812 93

The objective of this paper was to determine whether intrathymic injection of retinal S-antigen (S-Ag) can prevent experimental autoimmune uveoretinitis (EAU) in Lewis rats. Lewis rats were injected intrathymically with 25-100 micrograms of S-Ag in 100 microliters split between thymic lobes. Controls received vehicle alone (PBS) or 100 micrograms of BSA. Animals were immunized two weeks later with 100 micrograms of S-Ag in CFA with or without pertussis toxin (0.5 micrograms/rat). Clinical ocular disease was confirmed by histopathology. Splenocytes and lymph node cells were assayed, in vitro, for their ability to proliferate in response to various concentrations of S-Ag. Furthermore, attempts were made to adoptively transfer protection to naive rats using spleen cells from intrathymically injected animals and to adoptively transfer EAU to protected rats using Con A activated cells from affected animals. Intrathymic injection of S-Ag reduced the incidence of EAU in animals subsequently immunized with S-Ag and pertussis, and prevented it entirely in rats immunized in the absence of pertussis. Splenic and lymph node cells from intrathymically injected animals showed reduced reactivity to S-Ag compared to controls, suggesting that intrathymic S-Ag injection may have rendered them tolerant to this antigen. We were unable to adoptively transfer protection to naive rats, nor were intrathymically injected rats protected from EAU induced by the adoptive transfer of primed lymph node cells. These data demonstrate that intrathymic S-Ag injection can be an effective method for protection from EAU, apparently through the induction of immunological tolerance and not active suppression. The tolerance was not absolute and could be overcome by increasing the intensity of the antigenic challenge.
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PMID:Prevention of experimental autoimmune uveoretinitis by intrathymic S-antigen injection. 932 61

Bullous pemphigoid is an autoimmune blistering skin disease characterized by IgG autoantibodies targeting the skin basement membrane component type XVII collagen (BPAg2). To gain understanding of the disease's induction phase, we subcutaneously immunized adult BALB/c mice with peptides of human and/or the murine-equivalent BPAg2 pathogenic NC16A domain. Female mice were injected with peptides (human, murine, or combined human and murine), or PBS control emulsified in CFA, on a four-week interval. At the fourth and subsequent immunizations, all peptide-immunized mice were given murine peptides. Two weeks after the sixth immunization, ELISA detected IgG circulating autoantibodies against self peptides in 92% (47/51) of mice immunized with murine peptides; whereas none of the preimmune sera or the sera from PBS control-immunized mice reacted to the self peptides. In four mice their autoantibodies labeled mouse skin basement membrane. Breaking B-cell tolerance to BPAg2 sets the first step in dissecting the disease's induction phase.
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PMID:Characterization of BALB/c mice B lymphocyte autoimmune responses to skin basement membrane component type XVII collagen, the target antigen of autoimmune skin disease bullous pemphigoid. 1137 4

NK1.1(+) alpha beta T cells (NKT cells) regulate the Th1/Th2 balance in response to dietary Ag, which may be involved in regulation of oral tolerance. OVA-specific IgE and IgG(1) Ab levels were significantly lower following an i.p. injection of OVA (in CFA) in C57BL/6 mice orally given a single, high dose (25 mg) of OVA than in those orally given PBS. The oral tolerance was normally induced in Jalpha281(-/-) mice which lack Valpha14(+) NKT cells, suggesting that NKT cells are dispensable for induction of oral tolerance. Treatment with PGE(1) or PGE(2 )abrogated the oral tolerance in Jalpha281(+/+) mice; this abrogation was accompanied by an OVA-specific Th2-dominant response. The abrogation of oral tolerance by PGE(1 )was not evident in Jalpha281(-/-) mice. Treatment with PGE(1) induced an early increase in IL-4 production by liver NKT cells in normal mice and neutralization of the early IL-4 by administration of anti-IL-4 mAb abolished PGE(1)-induced abrogation of oral tolerance. These results suggest that liver NKT cells producing IL-4 are responsible for the down-regulation of oral tolerance that is caused by the PGE molecules.
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PMID:NKT cells are dispensable in the induction of oral tolerance but are indispensable in the abrogation of oral tolerance by prostaglandin E. 1259 47

Anti-prothrombin antibodies (aPT) are associated with thrombotic manifestations, and their association with reproductive failure is debatable. The aim of this study was to examine whether aPT could induce thrombosis and other clinical manifestations of the anti-phospholipid syndrome (APS). Mice were immunized with either prothrombin, beta2-glycoprotein-I (beta2GPI), or beta2GPI followed by prothrombin. The presence of clinical manifestation of APS, including thrombocytopenia, lupus anticoagulant and fetal resorption rates, was evaluated in all mice groups compared with nonimmunized mice. Thrombosis was studied in a novel ex-vivo model in which the aorta was sutured for 1 min and the presence or absence of visible thrombus was qualitatively evaluated. Immunized mice developed high autoantibody levels directed towards their immunizing autoantigens. The groups immunized with beta2GPI or beta2GPI/prothrombin, but not with prothrombin alone, developed prolonged aPTT, thrombocytopenia and increased fetal resorption rate. All prothrombin-immunized mice as well as most beta2GPI/prothrombin-immunized mice developed visible thrombus within the aorta. Some beta2GPI immunized mice developed very mild thrombus. None of the CFA/PBS-injected or the nonimmunized mice developed such thrombus. Active immunization with prothrombin or beta2GPI/prothrombin is associated with prothrombotic activity of blood in an ex-vivo model. This is the first direct evidence for thrombus induction by aPT.
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PMID:Anti-prothrombin antibodies cause thrombosis in a novel qualitative ex-vivo animal model. 1276 99

We used human monocyte-derived dendritic cells (DC) and Balb/c mice as models to establish the immunogenic and protective potential of formalin-inactivated Shigella spp. Incubation of DC with inactivated or live bacteria induced DC maturation and cytokine release. Mice immunized orally or intranasally with killed S. flexneri, S. sonnei, or S. dysenteriae developed IgG and fecal IgA titers to the homologous LPS. Following respiratory challenge with the live homologous organisms, 80-100% survival was seen in all vaccinated groups compared to negligible survival in mice given PBS. Oral or intranasal immunization with an inactivated S. flexneri 2a strain (CVD1203) expressing the CFA/I and CS3 antigens of enterotoxigenic Escherichia coli induced IgG responses to both heterologous antigens. These in vivo and in vitro data indicate that inactivated shigellae retain the ability to interact effectively with key antigen presenting cells and induce protective immune responses in mice.
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PMID:Vaccine potential for inactivated shigellae. 1717 31

Regulatory T (T(reg)) cells show promise for treating autoimmune diseases, but their induction to elevated potency has been problematic when the most optimally derived cells are from diseased animals. To circumvent reliance on auto-antigen reactive T(reg) cells, stimulation to vaccine antigens (Ags) may offer a viable alternative while maintaining potency to protect against proinflammatory diseases. Our Salmonella vaccine expressing colonization factor Ag I (CFA/I) possesses anti-inflammatory properties, evident by elevated Th2 cell responses, reduced inflammatory cell infiltrates in the Peyer's patches, and an absence of proinflammatory cytokine production by infected macrophages. Given these findings, we hypothesized whether this vaccine would be protective against experimental autoimmune encephalomyelitis (EAE). As such, Salmonella-CFA/I protected in both prophylactic and therapeutic paradigms against proteolipid protein (PLP(139-151))-mediated EAE in SJL mice. The protected mice showed significantly reduced clinical disease and subsequent resolution when compared to PBS-treated controls. Histopathological studies showed reduced demyelination and no inflammation of spinal cords when compared to PBS- or Salmonella vector-treated mice. To ascertain whether the observed immune deviation was in part supported by T(reg) cells, analysis revealed involvement of FoxP3(+) CD25(+) CD4(+) T cells. Adoptive transfer of induced TGF-beta (+) T(reg) cells from vaccinated mice showed complete protection against PLP(139-151) challenge, but not by naive T(reg) cells. Partial protection to EAE was also achieved by the adoptive transfer of CD25(-) CD4(+) T cells, suggesting that Th2 cells also contributed. Thus, these data show that T(reg) cells are induced by oral vaccination with Salmonella-CFA/I contributing to the efficacious treatment of autoimmune disease.
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PMID:Tolerance in the absence of autoantigen. 1789 47


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