Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study a possibility was examined that the specific antigen might inhibit antibody forming cells in order to know whether a non-T-cell-dependent mechanism of self-tolerance is present or not. If an autoantigen inhibits autoantibody forming cells, this inhibition may be one of the non-T-cell-dependent mechanisms of self-tolerance. Spleen cells from mice which were immunized with sheep red blood cells (SRBC) were incubated with SRBC and after an hour incubation erythrocytes added were removed. After 4 and 8 hr incubation, the plaques against SRBC were assayed by the plaque method. 1) After 8 hr incubation, SRBC reduced the plaque count to about 60% of the control aliquot incubating spleen cells with C3H mouse red blood cells. 2) This inhibition required 1% SRBC suspension, but despite increase in its concentration to more than 1% the degree of the inhibition remained constant. 3) This inhibition seemed to require neither T cells, macrophages nor the cells which display the cytotoxic activity in the antibody dependent cell-mediated cytotoxicity.
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PMID:Antigen inhibition on antibody forming cells at the level of effector cell. 78 97

Immunization protocols that induce high levels of delayed-type hypersensitivity are often associated with low levels of antibody production, whereas alternative immunization strategies can produce the opposite effect. This reciprocal relationship appears to depend, at least in part, on the fact that T cell-derived lymphokines that are predominantly involved in one type of response inhibit the development of those T cells that promote the alternative one. Such a regulatory mechanism is likely to be bistable in that whenever one form of response is established, spontaneous development of the alternative one will be inhibited. We have applied this concept to the control of a cell-mediated autoimmune disease in rats. By covalently linking the autoantigen to anti-IgD antibody, we have targeted it to B cells for presentation to antigen-specific T cells. This form of presentation favors antibody production and may be expected to antagonize the cell-mediated disease-inducing response to the same antigen. To test this hypothesis, use was made of the fact that experimental allergic encephalomyelitis (EAE), when induced with the encephalitogenic peptide of guinea pig myelin basic protein, is purely a cell-mediated disease. The experiments show that Lewis rats, immunized with the peptide in its encephalitogenic form, were protected from disease when simultaneously injected with the peptide coupled to anti-IgD monoclonal antibodies. Control experiments showed that neither peptide nor anti-IgD alone were protective, and the peptide covalently coupled to irrelevant antibodies also failed to protect. Spleen cells from animals protected from disease by the anti-IgD-peptide conjugate, when activated in vitro with the encephalitogen, were able to transfer EAE to naive recipients. The results demonstrate that a cell-mediated immune response can be controlled by appropriate targeting of the specific antigen without inducing T cell anergy and suggest a potential strategy for preventing autoimmune diseases that are essentially cell-mediated in type.
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PMID:Targeting autoantigen to B cells prevents the induction of a cell-mediated autoimmune disease in rats. 174 Jun 60

The production of antibodies to nucleic acids, and in particular to DNA, has been implicated in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). However, little is known about the conditions under which DNA is immunogenic, particularly in well-characterized in vitro systems. Therefore, we examined whether a source of cytokines, in conjunction with D-DNA, permitted a polyclonal or antigen-specific B-cell response. Spleen cells from MRL +/+ SLE-prone mice were incubated with supernatant from concanavalin A-stimulated spleen cells (Con A SN, a source of cytokines) and D-DNA. A potent antibody response developed to guanosine (GU) and D-DNA but not to fluorescein (FL), using as little as 10 ng D-DNA in conjunction with Con A SN. In order to further examine the cellular requirements for D-DNA to be immunogenic, populations of B cells which bound GU (an immunodominant epitope of DNA) or an irrelevant FL-binding population were purified and incubated with DNA and Con A SN. Interestingly, GU-binding, but not FL-binding B cells could be triggered by D-DNA derived from calf thymus, a result suggesting that DNA was not acting simply as a polyclonal B-cell activator. D-DNA optimally triggered GU+ B cells within a narrow dose range similar to many thymus-independent Type II antigens with repetitive determinants. If DNA were truly an autoantigen, then DNA derived from the MRL +/+ mouse should be capable of triggering GU-binding B cells. When this hypothesis was tested, D-DNA, but not N-DNA, functioned as a potent immunogen. These experiments document the ability of DNA to act as a specific immunogen and suggest that, under appropriate conditions, nucleic acid may induce autoantibody production in vivo.
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PMID:DNA is a potent immunogen for spleen cells and for guanosine-binding B lymphocytes. 245 1

Experimental autoimmune orchitis (EAO) developed in (C57Bl/6Cr x A/JCr)F1 mice 3-4 months after neonatal thymectomy (Tx) without any sensitization. The age of Tx was critical for induction of EAO: Tx at day 3 (Tx-3) was effective, but Tx at day 0 or day 7 was not effective. This lesion resulted in atrophy of the testis and was characterized by disappearance of mature sperms, formation of multinuclear giant cells in seminiferous tubules and infiltration of lymphocytes in the stroma. Epididymitis was observed prior to the development of EAO. Presence of circulating autoantibody(s) against sperms (ASA) was demonstrated by indirect immunofluorescence. The acrosomal area of mature sperms, but not of immature spermatids, was strongly. The incidence of EAO and titre of ASA increased when Tx-3 mice were unilaterally vasectomized (Vx). The majority of mice with high titres of circulating ASA were sterile. Epididymitis and orchitis could be prevented in Tx-3 mice by injection of adult spleen cells on day 4. The most effective source was normal male. Spleen cells from normal female donors and day-0 orchidectomized (Orx) donors were less effective, while those of Tx-3 male and female donors failed to prevent epididymis and orchitis. The cell population in normal male spleen effective in preventing epididymitis was shown to be a T cell population (Thy 1+, Ig-) by experiments with respective antisera treatment. These results showed that sensitization with sperm autoantigen occurred in the epididymis after Tx-3, more efficiently after Tx-3 plus unilateral Vx, and that this autosensitization was prevented by a specific suppressor T cell population, which was present in normal males but absent in Tx-3 mice.
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PMID:Experimental autoimmune orchitis after neonatal thymectomy in the mouse. 703 91

Human epidemiological studies delineated early exposure to intact dietary protein (e.g., most infant formulas) as an environmental risk factor for the development of IDDM. The Trial to Reduce IDDM in the Genetically at Risk (TRIGR), an international IDDM prevention trial, has been designed to determine if avoidance of intact dairy protein in high-risk infants < or =6 months of age can reduce the subsequent diabetes incidence. We here studied the casein hydrolysate-based trial diet (Nutramigen) in NOD mice. When given either continuously or for 10 weeks after weaning, the test diet was highly effective in preventing autoimmune diabetes (32-week incidence: 4.6 vs. 58.8%) and in preserving pancreatic insulin levels, with little effect on islet inflammation. Spleen cells from protected NOD mice failed to adoptively transfer diabetes into irradiated syngeneic recipients. When co-transferred with splenocytes from diabetic donors, cells from diet-protected mice inhibited adoptive diabetes transfer (incidence 50 vs. 94%, P < 0.001). T-cell reactivity to the islet cell autoantigens ICA69 (islet cell antigen 69) and GAD65 developed only in diabetic recipients of spleen cell grafts, indicating that diabetes protection extends to more than one autoantigen. In protected mice, ICA69 T-cell reactivity was not detectable spontaneously nor after priming with this autoantigen; however, priming with the cross-reactive non-self-antigen bovine serum albumin recruited T-cells responsive to ICA69. Thus, diabetes prevention with the clinical trial diet is effective in NOD mice, where it affects some T-cell repertoires and allows development of regulatory cells that interfere with destructive autoimmunity.
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PMID:Immunological aspects of nutritional diabetes prevention in NOD mice: a pilot study for the cow's milk-based IDDM prevention trial. 907 94

Autoimmune pancreatitis (AIP) is a heterogeneous autoimmune disease in humans characterized by a progressive lymphocytic and plasmacytic infiltrate in the exocrine pancreas. In this study, we report that regulatory T cell-deficient NOD.CD28KO mice spontaneously develop AIP that closely resembles the human disease. NOD mouse AIP was associated with severe periductal and parenchymal inflammation of the exocrine pancreas by CD4(+) T cells, CD8(+) T cells, and B cells. Spleen CD4(+) T cells were found to be both necessary and sufficient for the development of AIP. Autoantibodies and autoreactive T cells from affected mice recognized a approximately 50-kDa protein identified as pancreatic amylase. Importantly, administration of tolerogenic amylase-coupled fixed spleen cells significantly ameliorated disease severity, suggesting that this protein functions as a key autoantigen. The establishment and characterization of this spontaneous pancreatic amylase-specific AIP in regulatory T cell-deficient NOD.CD28KO mice provides an excellent model for the study of disease pathogenesis and development of new therapies for human autoimmune pancreatitis.
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PMID:Spontaneous development of a pancreatic exocrine disease in CD28-deficient NOD mice. 1852 43

Autoimmunity and inflammation are controlled in part by regulatory B cells, including a recently identified IL-10-competent CD1d(high)CD5(+) B cell subset termed B10 cells that represents 1-3% of adult mouse spleen B cells. In this study, pathways that influence B10 cell generation and IL-10 production were identified and compared with previously described regulatory B cells. IL-10-competent B cells were predominantly CD1d(high)CD5(+) in adult spleen and were the prevalent source of IL-10, but not other cytokines. B10 cell development and/or maturation in vivo required Ag receptor diversity and intact signaling pathways, but not T cells, gut-associated flora, or environmental pathogens. Spleen B10 cell frequencies were significantly expanded in aged mice and mice predisposed to autoimmunity, but were significantly decreased in mouse strains that are susceptible to exogenous autoantigen-induced autoimmunity. LPS, PMA, plus ionomycin stimulation in vitro for 5 h induced B10 cells to express cytoplasmic IL-10. However, prolonged LPS or CD40 stimulation (48 h) induced additional adult spleen CD1d(high)CD5(+) B cells to express IL-10 following PMA plus ionomycin stimulation. Prolonged LPS or CD40 stimulation of newborn spleen and adult blood or lymph node CD1d(low) and/or CD5(-) B cells also induced cytoplasmic IL-10 competence in rare B cells, with CD40 ligation uniformly inducing CD5 expression. IL-10 secretion was induced by LPS signaling through MyD88-dependent pathways, but not following CD40 ligation. LPS stimulation also induced rapid B10 cell clonal expansion when compared with other spleen B cells. Thereby, both adaptive and innate signals regulate B10 cell development, maturation, CD5 expression, and competence for IL-10 production.
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PMID:The development and function of regulatory B cells expressing IL-10 (B10 cells) requires antigen receptor diversity and TLR signals. 1949 69