Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Immune Tolerance”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed2005

[Receptor selection and B cell immune tolerance].

The immune system of mammalian has developed sophisticated mechanism to deal with diverse unknown antigens by random rearrangement of V, D and J antigen gene fragments. The immune self-tolerance is the mechanism to avoid self-destruction by the gene rearrangement generated autoreactive lymphocytes. Until recently it was believed that autoreactive lymphocytes are either deleted or rendered unable to respond by the supposed cell or clone selection mechanism. However, recent findings from a number of laboratories suggest instead of cell selection but receptor selection plays an essential role in immune self-tolerance. Receptor selection is carried out by secondary or nested rearrangement of antigen receptor gene fragments, and can occur at different stages of lymphocyte differentiation. Furthermore, secondary rearrangement of receptor gene also plays an important role in shaping immune response after the interaction of receptor with antigen by altering its specificity.

Autoimmune Diseases↗
PubMed2001

The Immune Tolerance Network: tolerance at the crossroads.

Immune tolerance therapies are designed to reprogramme immune cells in a highly specific fashion in order to eliminate pathogenic responses but preserve normal immune function. A concept that has tantalized immunologists for decades, tolerogenic therapies would replace current lifelong immunosuppressive regimens and their often debilitating side-effects with short-term immunosuppressive regimens and their often debilitating side-effects with short-term, effective cures. Significant advances have been made over the past decade that have provided a more detailed understanding of the molecular events associated with T-cell recognition and activation. Unprecedented opportunities to test these approaches in a variety of human diseases have now emerged. As a result of these advances, the Immune Tolerance Network (ITN), a group of 70 expert immunologists spanning multiple disciplines, has been created to identify and promote the use of tolerogenic therapies in the clinic. Using a unique interactive approach designed to speed the development of clinical tolerance therapies, the ITN is examining new and innovative therapeutic approaches and bioassays in a range of autoimmune diseases and transplantation settings, as well as asthma and allergies. This work has been funded by the National Institutes of Health (in collaboration with the Juvenile Diabetes Foundation International).

Asthma↗
PubMed2005

Involvement of intestinal dendritic cells in oral tolerance, immunity to pathogens, and inflammatory bowel disease.

Dendritic cells (DCs) are composed of a family of cells, now recognized to be essential for innate and acquired immunity. DCs at mucosal surfaces have a particular capacity to induce the differentiation of regulatory T cells producing interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) in the steady state (non-infected, non-immunized), yet they retain the capacity to induce effector T cells in response to invasive pathogens. This decision between the induction of active immunity and tolerance will depend on the subpopulation of DC involved and the surface receptors engaged during DC activation and T-cell priming. The local microenvironment will likely play an important role both in defining the DC phenotype and in providing direct signals to responding T cells. Furthermore, DCs in organized mucosal lymphoid tissues preferentially induce the expression of CCR9 and alpha4beta7 on T cells, which results in T-cell homing to the intestinal lamina propria. Finally, DCs may play an important role in the maintenance of abnormal intestinal inflammation either by driving pathogenic T-cell responses in mesenteric lymph nodes or by acting to expand or maintain pathogenic T cells locally at sites of inflammation. In this review, a brief discussion of general issues of DC biology that are pertinent to mucosal immunity is followed by a more in-depth discussion of the phenotype and function of DC populations in the intestine.

Animals↗
PubMed2004

Does maternal immunoglobulin E decrease with increasing order of live offspring? Investigation into maternal immune tolerance.

BACKGROUND: Identifying the protective effect of a higher number of siblings is a significant finding in understanding the aetiology of allergic sensitization, asthma, eczema, and hayfever. Knowledge about causes behind the sibling effect may allow us to prevent atopic manifestations. OBJECTIVE: We tested the hypothesis that rising order of live offspring increases maternal immune tolerance (immune non-reactivity) against allergens. To this end, we investigated whether maternal IgE levels are associated with the number of live offspring. METHODS: In a cohort of 1456 newborns recruited between January 1989 and February 1990 on the Isle of Wight, UK, we determined maternal and cord serum IgE, and the order of live offspring. The data were analysed by means of linear and path analysis. RESULTS: Maternal and cord serum IgE were available in 820 mother-infant pairs with birth order information. We found that the number of live offspring significantly reduces maternal IgE. The decline was more prominent in mothers with atopy (n=268). The geometric means of IgE after the first, second, and third or higher delivery were 74.4, 66.6, and 43.0 kU/L, respectively. Findings of path analysis suggest a significant direct effect of birth order on maternal IgE, but no direct effect of birth order on cord serum IgE. CONCLUSION: The findings support that maternal immune tolerance against allergens may increase with increasing order of live offspring and thus pass on a lower risk of developing atopy in children of higher birth order.

Adult↗
PubMed1994

Generation of a murine monoclonal antibody to normal mammary epithelium using mice rendered immune-tolerant to malignant mammary epithelium.

A monoclonal antibody (MAb) that distinguishes normal from malignant mammary epithelia in tissue or cell lines was generated using a procedure that involved immune-tolerization before immunization. Immune-tolerance to two transformed mammary epithelial cell lines (MCF.7 and MDA.MB.231 cell lines combined) was induced in neonatal mice within 24 hr of birth. Successful induction of immune-tolerance was determined by an indirect immunohistological method, testing sera from mice against the tolerogen (i.e., the MCF.7 and MDA.MB.231 cell lines). Mice lacking antibodies in their sera against the immune-tolerogen were subsequently immunized with an extract of normal breast epithelium. One mouse was selected for hybridoma production based on evidence of serum antibody that showed reactivity with normal mammary epithelial cells (MEC) but not with invasive breast carcinoma cells, as determined by an indirect immunohistological method. Spleen cells from the selected mouse were fused with a mouse myeloma cell line to generate MAb. After extensive screening, one MAb was further studied on the basis of reactivity with normal MEC in tissue and absence of staining of malignant MEC in tissue or tumorigenic MEC lines. This test of specificity of reactivity revealed that the antigen detected by the specific antibody was expressed on the apical plasma membrane of normal glandular epithelia that included breast, cervix, colon, lung, pancreas, and stomach, but not on their malignant counterparts in tissue sections. The antigen recognized by the MAb was termed luminal epithelial antigen with an apparent MW of 92 KD (LEA.92). This study illustrates the practical usefulness of the immune-tolerization/immunization approach in the generation of antibodies with particular specificity requirements, as in the identification of an antigen that is differentially expressed in two tissues (e.g., normal and malignant) which otherwise have a multiplicity of antigens in common.

Adult↗
PubMed2006

[Dendritic cells and transplantation immune tolerance--review].

Dendritic cells (DC) play an important roles in the maintenance of central immune tolerance and peripheral immune tolerance. DC can be involved in formation of autoimmune tolerance by many mechanisms and demonstrate strong plasticity, so that DC become hot issue in the research of transplantation tolerance recently. In this article the DC typing and its role, the indirect pathway of DC-inducing immune tolerance, the F1t3L and apoptotic cell role, the modified DC by genetic engineering and the immune inhibitors were summarized.

Dendritic Cells↗
PubMed2002

The North American Immune Tolerance Registry: practices, outcomes, outcome predictors.

The North American Immune Tolerance Registry was initiated to study of immune tolerance (ITT) in Canada and the United States with respect to: 1) therapeutic regimens in use for haemophilia A (HA) and B (HB) inhibitor patients; 2) therapeutic outcomes; 3) potential predictors of successful outcome and 4) complications of therapy. Data on 188 ITT courses was collected by questionnaire from 60 haemophilia centers from 1993-99. Among the completed courses, the overall success rate was 70% (115/164) for all HA and 31% (5/16) for all HB. Outcome parameters noted to be predictive of ITT success for all HA were 1) pre-ITT induction (p = 0.003), 2) ITT peak (p = 0.007) and 3) historical pre ITT peak (p = 0.04) inhibitor titres. An inverse correlation between total daily dose (units/kg/day) and success: (80% with under 50; 71% with 50-99; 73% with 100-199; and 41% with > or = 200, p = 0.01) was found. Outcome predictors were not evaluable for HB, although adverse reactions to therapy, including nephrotic syndrome, and access complications were more common among failed courses. Infection most often complicated the use of access catheters. These results are discussed within the context of the international ITT registry and upcoming prospective ITT study.

Canada↗
PubMed1995

Low-dose immune tolerance induction in hemophilia A patients with inhibitors.

In patients with hemophilia A and inhibitory alloantibodies against factor VIII, various dosage schedules are used to obtain immune tolerance. In this study, we have evaluated the results of 13 years of low-dose immune tolerance induction and factors that are predictive of a positive result. The effect of immune tolerance induction in relation to age at inhibitor development, number of exposure days, age at start of therapy, maximum inhibitor titer, factor VIII products involved, and virologic status were determined. We evaluated 24 patients with severe hemophilia A and inhibitors who were treated with regular infusions with low-dose (25 U/kg every other day) factor VIII to obtain immune tolerance. In 21 of 24 patients (87%), immune tolerance induction was successful. The response time was determined by two factors: the highest inhibitor level and the age at inhibitor development. In patients with maximum inhibitor levels of less than 40 Bethesda units (BU)/mL, immune tolerance was obtained sooner than in patients with inhibitor levels exceeding 40 BU/mL (P = .005). Patients in whom an inhibitor developed before the age of 2.5 years also tended to have a quick immune response (P = .014). Immune tolerance with low-dose factor VIII is often successful in hemophilia A patients with inhibitors. Young children and patients with maximum inhibitors of less than 40 BU/mL show a relatively rapid response.

Adolescent↗
PubMed2006

The role of immune tolerance in asthma pathogenesis.

Immune-mediated tolerance encompasses a wide spectrum of mechanisms that can prevent unnecessary and potentially harmful inflammatory responses. An increasing number of scientific publications provide proof for the concept that an impairment of immune-tolerance mechanisms might be causally related to the development of unwanted Th2-driven, allergen-induced airway diseases. In this review, we discuss immune tolerance and the evidence supporting its role in asthma pathogenesis.

Animals↗
PubMed2000

T cell-independent rescue of B lymphocytes from peripheral immune tolerance.

Autoimmunity arises when immune tolerance to specific self-antigens is broken. The mechanisms leading to such a failure remain poorly understood. One hypothesis proposes that infectious agents or antigens can break B or T lymphocyte self-tolerance by expressing epitopes that mimic self. Using a transgenic immunoglobulin model, we show that challenge with self-mimicking foreign antigen rescues B cells from peripheral tolerance independent of T cell help, resulting in the accumulation of self-reactive cells in the lymph nodes and secretion of immunoglobulins that bind to a liver-expressed self-antigen. Therefore, our studies reveal a potentially important mechanism by which B lymphocytes can escape self-tolerance.

Animals↗
PubMed1998

Induction of immune tolerance in adult rabbits undergoing heterotopic cardiac transplantation.

OBJECTIVE: To induce experimental immune tolerance in rabbits and observe its effects on heterotopic cardiac transplantation. METHODS: Donor's splenic lymphocytes pretreated with platinum metal chelator were injected into the recipient's mesenteric-portal vein. Cyclosporin A was perfused through the donor's heart. RESULTS: The injection of donor's splenic lymphocytes before transplantation could significantly prolong the survival time of the heterotopically transplanted heart. The effect of two injections was better than that of one. Radioactive tracer studies showed that the 99mTc-HMPAO tagged lymphocytes injected into the recipient rabbit were later concentrated in the liver, though initially they were distributed in multiple organs. The induced immune tolerance was antigen-specific, and it neither affect the other immune functions of the lymphatic system prominently nor exert any harmful effect on the recipient's liver and renal functions. The perfusion of cyclosporin A through the donor heart could block the glycosyl groups, such as D-glucose, D-mannose or N-acetyl-galactosamine on the surface of the myocardial cells, thus might change the antigenic expression, effectively preventing rejection of the graft by the host, and might be considered as a new method to block graft rejection in cardiac transplantation. The combined use of the above-mentioned two methods acted on both the host and the donor, thus reducing the exposed antigens on the donor organ as well as the immune reaction against the donor antigens, and resulting in synergistic effect in inducing immune tolerance in adult rabbits, and resulting in relatively long-term survival of transplanted hearts. CONCLUSION: This report may provide the experimental basis for inducing immune tolerance in clinical transplantation.

Animals↗
PubMed2004

[The effect of splenic lymphocytes from oral immune tolerance rats on activity of NF-kappaB p65 in glomerular mesangial cells].

AIM: To explore the effect of splenic lymphocytes from oral immune tolerance rats on NF-kappaB p65 activity in glomerular mesangial cells. METHODS: 10 female Wistar rats with 6-8 weeks of age were divided randomly into two groups, 5 rats for each group. The rats of one group were given through intragastric feeding with 2 mL Fx1A antigen to induce oral immune tolerance, and the rats of the other group only with PBS (as control group). Two weeks later, the rats were sacrificed, and then their spleens were excised and lymphocytes were separated routinely for antigen-specific lymphocytes reaction. The culture supernatants of splenic lymphocytes from oral immune tolerance rats were prepared. The IL-10 level in the supernatants was detected by sandwich ELISA. After the cultured mesangial cells were stimulated with high dose of insulin, the culture supernatants of rat's splenic lymphocytes were added to insulin-treated mesangial cells. Twenty-four hours later, the NF-kappaB p65 activity in mesangial cells was detected by immunohistochemical staining and sandwich ELISA. RESULTS: As compared with control group, the proliferation reaction of splenic lymphocytes from oral immune tolerance rats was inhibited obviously, and IL-10 level in splenic lymphocyte culture supernatants from the tolerance rats rose markedly (P<0.01). NF-kappaB p65 activity induced by insulin in mesangial cells was inhibited by culture superatants of splenic lymphocytes from oral immune tolerance rats (P<0.05). CONCLUSION: NF-kappaB p65 activity in mesangial cells may be inhibited by IL-10 secreted by splenic lymphocytes from the oral immune tolerance rats.

Animals↗
PubMed2005

Induction of human papilloma virus E6/E7-specific cytotoxic T-lymphocyte activity in immune-tolerant, E6/E7-transgenic mice.

Despite promising preclinical results of various therapeutic anticancer immunization strategies, these approaches may not be effective enough to eradicate tumors in cancer patients. While most animal models are based on fast-growing transplantable tumors, malignancies in, for example, cervical cancer patients in general develop much more slowly, which may lead to immune suppression and/or immune tolerance. As a consequence, the immunomodulating signal of any therapeutic immunization regimen should be sufficiently potent to overcome this immunocompromised condition. In previous studies, we demonstrated that an experimental vaccine against human papillomavirus (HPV)-induced cervical cancer, based on Semliki Forest virus (SFV), induces robust HPV-specific cellular immune responses in mice. Now we studied whether this strategy is potent enough to also prime a cellular immune response in immune-tolerant HPV transgenic mice, in which CTL activity cannot be induced using protein or DNA vaccines. We demonstrate that, depending on the route of immunization, SFV-expressing HPV16 E6 and E7 indeed has the capacity to induce HPV16 E7-specific cytotoxic T cells in HPV-transgenic mice.

Animals↗
PubMed2005

The level of maternal immune tolerance and fetal maturity.

OBJECTIVES: Fetal maturity does not seem to be directly connected with the phenomenon of immune tolerance during pregnancy although the fetal maturation influences the process of initiation of the labor at term finishing the immune tolerance during pregnancy. CAP and RCAS1 are expressed by the trophoblast cells and afterwards by the placenta, these proteins are able to modulate the maternal immune response. MATERIALS AND METHODS: 160 patients were randomly selected to our study. The patients were divided into two groups using K score according to the newborn's maturity: maturated and not fully maturated. Within the groups of matured and not fully matured newborns the subgroups were selected according to the type of the labor: spontaneous or induced. The oxytocinase plasma activity was established in plasma samples obtained from pregnant women a few days before delivery. The placental RCAS1 relative amount was assessed by Western blot analysis. RESULTS: The differences in oxytocinase plasma level with respect to the fetal maturity were identified in our study however no RCAS1 expression changes were found regarding the fetal maturation. We determined the alterations in RCAS1 expression with respect to the occurrence of clinical symptoms of the spontaneous beginning of the labor in maturated and not-fully maturated groups of newborns. CONCLUSIONS: Oxytocinase seems to be a useful marker of normal fetal development. The assessment of RCAS1 in placenta directly after delivery appears to indicate the level of maternal immune tolerance during the labor initiation. The level of the immune tolerance at the moment of the delivery drops independently of the fetal maturity.

Actins↗
PubMed2006

Does our current understanding of the molecular basis of immune tolerance predict new therapies for autoimmune disease?

The creation of specific immune tolerance has often been referred to as the ultimate goal of immunotherapy, because it would allow autoimmune disease to be reversed without the need for nonspecific and potentially harmful immunosuppressive therapy. Studies performed during the past decade have been immensely fruitful in terms of advances in our understanding of the cellular and molecular mechanisms of immune tolerance, and have paved the way for successful exploitation of these mechanisms for therapeutic purposes. Important developments include an increased understanding of central and peripheral tolerance, and treatment strategies that mimic the mechanisms behind deletion of self-reactive cells, the identification of crucial gene products that are involved in the induction of anergy, and the characterization of regulatory T cells and protocols for their induction and expansion for therapeutic applications. These landmarks of immune-tolerance research are summarized and their potential use in the immunotherapy of autoimmune disease discussed.

Autoimmune Diseases↗