Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have used the mouse model of experimental autoimmune thyroiditis (EAT) to examine the hypothesis that the strengthening of self-tolerance to thyroglobulin by exogenous mouse thyroglobulin (MTg) or stimulation of endogenous MTg secretion by thyroid-stimulating hormone (TSH) is correlated with the length of time MTg rises above the normal range. Bacterial lipopolysaccharide (LPS) treatment increases the initial half-life of MTg from about 3 hr to about 5 hr, probably interfering with its clearance by the mononuclear phagocytic (reticuloendothelial) system. By pretreating mice with LPS, a subtolerogenic MTg dose is rendered tolerogenic. Similarly the effect of TSH infusion by osmotic minipumps, which stimulates MTg secretion and also strengthens tolerance to MTg, can be enhanced by injecting LPS shortly after pump implantation. The resulting increase in MTg level (due to delayed clearance of MTg) is greater than that from TSH alone and suppresses further the animals' susceptibility to disease induction by MTg and adjuvant. Moreover, resistance following pretreatment with LPS and subtolerogenic MTg is mediated by CD4+ suppressor T cells, as shown recently for the suppression in mice given high doses of tolerogenic MTg. These experiments are in full agreement with the hypothesis and confirm that small increases in circulating MTg concentrations, which could occur physiologically, can be effective in protecting against EAT induction.
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PMID:Resistance to experimental autoimmune thyroiditis is correlated with the duration of raised thyroglobulin levels. 164 52

Spleen cells from CBA/J mice immunized with mouse thyroglobulin (MTg) and the adjuvant lipopolysaccharide induce experimental autoimmune thyroiditis (EAT) after transfer to recipient mice if they are first activated in vitro with MTg. EAT induced by cells cultured with MTg is generally moderate in severity and is characterized by a thyroid infiltration consisting primarily of mononuclear cells. Addition of the anti-interleukin 2 receptor (IL-2R) monoclonal antibodies (mAbs) M7/20, 3C7, or 7D4 to spleen cell cultures with MTg resulted in a cell population capable of inducing a more severe type of EAT characterized by extensive follicular destruction, granuloma formation, and the presence of multinucleated giant cells. Recipients of cells cultured with MTg and anti-IL-2R mAb also had higher anti-MTg autoantibody responses than recipients of cells cultured with MTg alone. Activation of cells capable of transferring severe granulomatous EAT and increased anti-MTg autoantibody responses required both MTg and M7/20 in culture and required addition of M7/20 within the first 8 h of the 72-h culture period. CD4+ T cells were required for the expression of both the severe granulomatous EAT lesions and the mononuclear cell infiltrates typically observed in murine EAT. The increased anti-MTg autoantibody responses in recipients of cells cultured with MTg and anti-IL-2R mAbs were not restricted to a particular immunoglobulin G (IgG) subclass and included antibody of the IgG1, IgG2A, and IgG2B subclasses. These results suggest that a subset of CD4+ T cells capable of inducing severe granulomatous EAT and increased anti-MTg autoantibody responses is preferentially activated when cells are cultured in the presence of anti-IL-2R mAb. Anti-IL-2R mAb may either prevent activation of cells that induce classical lymphocytic EAT or prevent activation of cells that normally function to downregulate EAT effector T cell activity.
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PMID:Induction of severe granulomatous experimental autoimmune thyroiditis in mice by effector cells activated in the presence of anti-interleukin 2 receptor antibody. 167 46

Genetically susceptible mice become resistant to experimental autoimmune thyroiditis (EAT) induction with mouse thyroglobulin (MTg) and lipopolysaccharide after pretreatment with deaggregated MTg (dMTg). Recent work showed this suppression to be mediated by CD4+ suppressor T cells (Ts). To study Ts action in vivo, we used a rat IgG2a monoclonal antibody (mAb), YTS 177.9, which modulates CD4 antigen in vivo without depleting CD4+ cells. Initial studies showed that after two 1-mg doses of mAb 7 days apart, extensive CD4 antigen modulation of peripheral blood leukocytes occurred within 4 days. Mice given CD4 mAb 24 hr before dMTg (2 doses, 7 days apart) were resistant to EAT induction when immunized with MTg and LPS 20 days later. Also, anti-rat IgG2a titers were reduced following challenge with heat-aggregated rat IgG2a compared to controls. Subsequent analysis of serum in CD4 mAb-treated animals revealed that mAb was present in the circulation for 14 days. Moreover, mice given CD4 mAb and dMTg, then challenged after only 10 days, when CD4 mAb was still circulating, developed a significantly higher incidence of thyroid damage than controls. These findings suggest that modulation of CD4 antigen does not interfere with Ts activation, but the presence of CD4 mAb, at the time of autoantigenic challenge, can interfere with tolerance to EAT induction. Thus, the direct relationship between the presence of CD4 mAb and inhibition of EAT suppression implicates a role for CD4 molecules in the mediation of suppression.
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PMID:Suppression in murine experimental autoimmune thyroiditis: in vivo inhibition of CD4+ T cell-mediated resistance by a nondepleting rat CD4 monoclonal antibody. 168 May 68

T cells from genetically susceptible mice developing experimental autoimmune thyroiditis (EAT) proliferate in response to restimulation with mouse thyroglobulin (MTg) in vitro. The in vitro-activated cells adoptively transfer EAT as well as differentiate into cells cytotoxic for syngeneic thyroid monolayers. To examine the kinetics of T cell subset infiltration and distribution in situ after adoptive transfer, we applied the avidin-biotin-peroxidase labeling technique to thyroid sections, utilizing rat monoclonal antibodies followed by a biotinylated rabbit anti-rat antibody. Female CBA donor mice were immunized with MTg and lipopolysaccharide. Their spleen cells were obtained 7 days later, cultured with MTg, and transferred into recipient mice. The thyroids were removed on Days 7, 10, and 14 after transfer and serially sectioned. The early phase of transferred EAT showed a higher percentage of L3T4+ cells compared to Lyt-2+ cells, yielding a ratio of 2.3 and total T cells of about 35%. By Day 10, both T cell subsets had increased to a total of about 56%. However, the relative increase was greater in the Lyt-2+ subset; the nearly doubled percentage was statistically significant, resulting in a downward shift in the subset ratio to 1.7. Little change in the in situ distribution was seen on Day 14. The percentages of F4/80+ (macrophage) population in lesions examined on Days 10 and 14 were fairly constant and B cell involvement was minimal. These findings illustrate the pathogenic role of both T cell subsets in adoptively transferred EAT and the time-dependent changes in their relative proportions leading to thyroid gland destruction.
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PMID:In situ analysis of T cell subset composition in experimental autoimmune thyroiditis after adoptive transfer of activated spleen cells. 229

Previous studies have shown that T cells from genetically susceptible mice developing experimental autoimmune thyroiditis (EAT) proliferate in response to restimulation with mouse thyroglobulin (MTg) in vitro and differentiate into cells cytotoxic for syngeneic thyroid monolayers. To examine further the effector cells involved in pathogenesis and the determinants on MTg responsible for their activation, spleen cells (SC) and lymph node cells (LNC) from mice immunized with MTg or human (H) Tg, and adjuvant (complete Freund's adjuvant (CFA) or lipopolysaccharide (LPS] were cultured in vitro with MTg or HTg. Control cultures were incubated with concanavalin A (Con A) or purified protein derivative (PPD). The in vitro-activated cells which proliferated in response to MTg, HTg, or Con A adoptively transferred thyroiditis to normal recipients, whereas cells transferred directly without in vitro culture were very ineffective. The capacity to transfer EAT was abrogated by irradiation (1500 R), and SC from CFA-immunized control mice which responded in vitro to PPD stimulation did not transfer thyroiditis. The serum titers of MTg autoantibodies were uniformly low and were not correlated with severity of disease. The localization of EAT-effector (precursor) cells depended upon the site of immunization; they were found in the spleens after inguinal (subcutaneous) or systemic (intravenous) immunizations, but were present in the popliteal lymph nodes after hind footpad injections. Both homologous MTg and heterologous HTg functioned as in vivo sensitizing antigen and in vitro activating antigen for each other; such cultured cells transferred thyroiditis in vivo and became cytotoxic for thyroid monolayers in vitro. These findings show that shared determinants are autoantigenic and thyroiditogenic, and support the hypothesis that EAT-effector cells responsible for initiating thyroid damage include cytotoxic cells.
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PMID:Activation of cytotoxic T cells and effector cells in experimental autoimmune thyroiditis by shared determinants of mouse and human thyroglobulins. 242 54

Experimental autoimmune thyroiditis (EAT) can be adoptively transferred to normal syngeneic recipients using spleen cells from susceptible strains of mice primed in vivo with mouse thyroglobulin (MTg) and lipopolysaccharide (LPS) following in vitro activation of spleen cells by culture with MTg. Irradiation of recipient animals markedly augments the severity of thyroiditis induced in this system. Irradiation of recipients does not alter the time course of the development of thyroiditis, nor does it alter the requirement for both in vivo priming and in vitro activation of spleen cells for the development of EAT. Spleen cells from EAT-resistant strains of mice (e.g., Balb/c) do not induce EAT in irradiated recipients. Irradiated recipients develop significant levels of anti-MTg antibodies while unirradiated recipients have little detectable antibody response. The augmenting effect of irradiation can be substantially reversed by transferring naive spleen cells to recipients prior to the transfer of MTg/LPS-primed in vitro-activated spleen cells. In addition athymic CBA/Tufts nude mice develop more severe EAT than CBA/Tufts nude/+ littermates following transfer of activated CBA/J spleen cells. These data suggest that natural suppressor cells may regulate the development of EAT at the effector cell level.
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PMID:Augmentation of transfer of experimental autoimmune thyroiditis (EAT) in mice by irradiation of recipients. 295 75

Susceptibility to experimental autoimmune thyroiditis (EAT) in the mouse is linked to the I-A subregion of the major histocompatibility complex. EAT can be induced in susceptible strains of mice by immunization with mouse thyroglobulin (MTg) and adjuvant. We have described a cell transfer system wherein spleen cells from EAT-susceptible CBA/J mice primed in vivo with MTg and lipopolysaccharide (LPS) can be activated in vitro with MTg to transfer EAT to naive syngeneic recipients. This cell transfer system was used to elucidate the cellular basis for the I-A restriction in EAT. While the cell active in transferring EAT was Thy 1+ I-A-, depletion of I-A+ cells from the in vitro culture prevented the activation of EAT effector T cells. MTg-pulsed mitomycin C-treated naive syngeneic spleen cells as antigen-presenting cells (APCs) could replace the I-A+ cells in vitro. Allogeneic (Balb/c) APCs were ineffective. Using APCs from several recombinant inbred strains of mice, it was shown that C3H/HEN and B10.A(4R) APCs were effective in activating MTg/LPS-primed CBA/J spleen cells to transfer EAT while B10.A(5R) APCs were ineffective. This maps the H-2 restriction to the K or I-A subregions. Addition of polyclonal anti-Iak or monoclonal anti-I-Ak or anti-L3T4 during in vitro activation inhibited both the generation of EAT effector cells and the proliferative response to MTg. Irrelevant anti-Ia reagents, monoclonal anti-I-Ek, and monoclonal anti-I-Jk were ineffective. Thus the I-A restriction in murine EAT appears to result from an I-A restricted interaction between Ia+ APCs and Ia- EAT effector T cells.
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PMID:The cellular basis for the Ia restriction in murine experimental autoimmune thyroiditis. 349 88

The role of humoral and cellular immune responses in the initiation and maintenance of autoimmune thyroiditis was investigated in mice immunized with syngeneic thyroid extract and Klebsiella O3 lipopolysaccharide (KO3 LPS) as an adjuvant. The transfer of spleen cells from hyperimmunized mice to 400R-irradiated syngeneic mice produced definite lesions in the thyroid glands, whereas the transfer of immune sera failed to do so. No lesions were induced in normal intact mice by the same transfer of sera and spleen cells from hyperimmunized mice. It was suggested that the induction of thyroiditis by immunization using KO3 LPS adjuvant is primarily due to cell-mediated immunity and that pretreatment of mice by X-irradiation is essential for production of the lesions. The role of X-irradiation in the induction of thyroiditis was discussed.
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PMID:Microbial adjuvant and autoimmunity. IV. The induction of thyroid lesions in syngeneic X-irradiated mice by the transfer of spleen cells from mice immunized with thyroid extract and Klebsiella O3 lipopolysaccharide. 375 93

By using a recently developed method for producing thyroiditis in mice consisting of implantation of a fresh thyroid gland into the peritoneal cavity or under the capsule of the kidney with subsequent injection of lipopolysaccharide, differences were shown in susceptibility of the target thyroid gland to autoimmune destruction and in antigenicity of the thyroid gland for induction of experimental autoimmune thyroiditis. Using recombinant congenic mice, the H-2 haplotypes of the target thyroid gland were found to be as important as those of the immune system in development of autoimmune thyroiditis. On the other hand, the H-2 haplotypes of the thyroid gland are unimportant for induction of autoimmune thyroiditis.
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PMID:The differences of susceptibility of the target thyroid gland to autoimmune thyroiditis and of antigenicity of thyroid gland for induction of experimental autoimmune thyroiditis. 378 53

Experimental autoimmune thyroiditis (EAT) can be induced in susceptible strains of mice by injection of mouse thyroglobulin (MTg) and adjuvant. Lymphocytes from immunized mice develop a proliferative response to MTg which generally correlates with the development of EAT. We utilize a cell transfer system wherein spleen cells from CBA/J mice primed with MTg and lipopolysaccharide (LPS) in vivo are activated by culture with MTg in vitro to transfer EAT to naive recipients. In vivo priming of CBA/J mice is required to develop an antigen specific proliferative response to MTg. This response is optimal between 48 and 90 hr of culture at an MTg concentration of 125-250 micrograms/ml. The correlation between proliferation and transfer of EAT is not absolute as primed Balb/c X CBA/J F1 and AKR lymphocytes do not proliferate detectably in response to MTg but can be activated to transfer EAT; primed Balb/c lymphocytes neither proliferate nor transfer EAT. Proliferation per se is not sufficient to activate cells to transfer EAT as culture with nonspecific mitogens is not effective in activating primed CBA/J spleen cells to transfer EAT. However, lymphoblasts generated during in vitro culture of primed CBA/J spleen cells with MTg are responsible for transfer of EAT; small lymphocytes are ineffective. We conclude that antigen specific proliferation in response to MTg is essential in activating lymphocytes in vitro to transfer EAT.
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PMID:The role of cellular proliferation in the induction of experimental autoimmune thyroiditis (EAT) in mice. 380 8


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