Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “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 649 records · Page 36Linked to original sources
PubMed1976

B cell tolerance induced by polymeric antigens. II. Effects of tolerance on hapten-binding lymphocyte levels in primary and secondary antibody responses.

Tolerogenic doses of hapten [2,4-dinitrophenyl (DNP)]-coupled type 3 pneumococcal polysaccharide (DNP-lys2.5-S3) totally abolished the anti-DNP rosette-forming cell (RFC) response to primary immunization with DNP-hemocyanin in mice, while lightly substituted antigen (DNP-lys0.6-S3) had little effect. Both antigens suppressed secondary anti-DNP RFC responses to DNP-KLH. Limiting doses of DNP-lys-S3 preferentially suppressed antibody-secreting cell levels, and had less effect on RFC. DNP-lys2.5-S3 was 500--1000-fold more potent in "blockading" primary RFC in vitro than DNP-lys0.6-S3, whereas both antigens were equally effective in blocking secondary RFC. These results suggest that the sensitivity of primed B lymphocytes to inactivation by DNP-lys-S3 is related to their high avidity for antigen. Furthermore, this appears to be largely due to a high density of immunoglobulin receptors on primed cells since the affinities of primary and secondary RFC for monovalent hapten were indistinguishable. Treatment of primarily immunized mice with DNP-lys2.5-S3 2 h before assay abolished 90% of RFC. Therefore, the reduction in RFC levels in tolerant mice may be due to cellular blockade by persisting tolerogen. However, it seems unlikely that simple blockade of antigen-reactive cells is the sole mechanism operative in this system.

Animals↗
PubMed1998

Mice expressing the E7 oncogene of HPV16 in epithelium show central tolerance, and evidence of peripheral anergising tolerance, to E7-encoded cytotoxic T-lymphocyte epitopes.

In order to derive mice which expressed both the E7 open reading frame transgene of human papillomavirus type 16 in skin and MHC class 1 restriction elements for several E7-encoded cytotoxic T-lymphocyte (CTL) epitopes, K14.HPV16E7 mice which express E7 in basal keratinocytes were crossed to the F1 generation with A2.1 Kb transgenic mice which express the MHC binding cleft domains of human HLA A*0201, and murine H-2b. F1 mice (denoted K14E7 x A2.1) expressed E7 in the thymus at least as early as 2-5 days before birth. Immunisation of FVB x A2.1 control mice (transgenic for HLA A*0201 and H-2b but not for E7), with two HLA A*0201-restricted epitopes of E7 and one H-2b-restricted CTL epitope of E7, gave strong primary CTL responses recognising epitope-pulsed or constitutively E7-expressing syngeneic target cells. In contrast, in immunised K14E7 x A2.1 mice, the CTL responses to the H-2b epitope and one of the HLA A*0201 CTL epitopes were strongly down-regulated, and to the other HLA A*0201 epitope, completely abolished, as demonstrated by percentage specific killing by bulk splenocyte cultures in cytotoxicity assays, and by CTL precursor frequency analysis. In thymus-transplanted bone marrow radiation chimeras in which the immune system of K14E7 x A2.1 mice was replaced by a FVB x A2.1 immune system, specific immunisation did not result in reemergence of strong E7-directed CTL responses. In agreement with these in vitro findings, specific immunisation failed to significantly alter the course of E7-associated tumour development in K14E7 x A2.1 mice. These data are consistent with a model of central deletional CTL tolerance to E7-encoded epitopes recognised in the context of two distinct MHC class 1 restriction elements, and with the possibility of peripheral T-cell anergy maintained by expression of E7 in the skin.

Amino Acid Sequence↗
PubMed1986

Tolerance to effects of morphine without cross tolerance to effects of clonidine on schedule-controlled behavior of pigeons.

Schedule-controlled responding was maintained under a multiple fixed-interval, fixed-ratio schedule in pigeons. Dose-related decreases in response rates were produced by clonidine (0.001-0.1 mg/kg) and morphine (0.3-5.6 mg/kg). Chronic administration of morphine produced (1) tolerance to effects of morphine, as evidenced by a decrease in potency of morphine and (2) sensitivity to opioid antagonists, as evidenced by an increase in potency of naloxone. Dose-effect curves for clonidine were not appreciably altered by chronic morphine administration.

Animals↗
PubMedDate not supplied

Glucose tolerance factor potentiation of insulin action in adipocytes from rats raised on a torula yeast diet cannot be attributed to a deficiency of chromium or glucose tolerance factor activity in the diet.

The nature of the dietary component responsible for adipocytes having the ability to respond to Glucose Tolerance Factor (GTF) was investigated. Rats were raised on either a control diet or one of three diets differing only in the protein source (torula yeast, brewer's yeast, or casein). Only in adipocytes from rats fed the torula yeast diet did a GTF fraction prepared from brewer's yeast potentiate the action of suboptimal concentrations of insulin in the incorporation of label from D-[1-14C]-glucose and D-[U-14C]-glucose into CO2 and fatty acids. It was concluded that this potentiation was not the result of a deficiency of GTF activity in torula yeast, because a GTF fraction prepared from torula yeast had similar insulin potentiating activity. Differences in response among diets were not owing to differences in levels of amino acids or owing to concentrations of 22 (Al, As, B, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mo, Na, Ni, P, Pb S, Se, Si, Sn, Sr, Zn) of the 23 trace elements investigated. The level of Mn was low in all diets, but particularly low in the torula yeast diet. Mn deficiencies have previously been implicated in perturbations of glucose metabolism, so that it is possible that this deficiency may be responsible for the effects attributed to the torula yeast diet.

Adipose Tissue↗
PubMed2000

Prope tolerance: a step in the search for tolerance in the clinic.

Following the demonstration by Knechtle and colleagues that profound T cell depletion in rhesus monkeys treated with a CD3 diphtheria immunotoxin resulted in tolerance to renal allografting, we have used a similarly depleting protocol that, in addition, depletes B cells in recipients of a cadaveric renal transplant. The humanized antiCD52 monoclonal antibody had a rapid depleting effect when given intravenously, 20 mg on days 0 and 1 after-renal transplantation, to 31 patients. At 48 hours after the second dose of low dose monotherapy cyclosporine (Neoral) was given to maintain blood levels averaging 100 ng/ml. Initially no other immunosuppression was given. With an average follow-up of 24 months all but one of the patients are alive, 29 with intact functioning grafts. There have been five rejection episodes, which responded to pulsed steroid treatment. One patient had a recurrence of her original disease. Two patients developed opportunistic infections, which responded to therapy; and one patient with severe heart failure at the time of surgery died from this condition after 11 months. Currently 29 patients are still on the original low dose cyclosporine monotherapy. The outcome in this cohort of patients has been encouraging, with efficacy that compares favorably to our conventional triple therapy but in most cases allows the patients to be steroid-free on low dose immunosuppressive monotherapy. The maintenance treatment is inexpensive and should be beneficial in the context of tight budgetary constraints worldwide. The patients who avoided steroids are pleased with this aspect of the protocol. A randomized trial comparing this treatment with standard therapy is planned.

Animals↗
PubMed1991

Comparison of isobutyl nitrate and isobutyl nitrite: tolerance and cross-tolerance to glyceryl trinitrate.

This study includes the first systematic comparison of an organic nitrate with the corresponding organic nitrite-isobutyl nitrate and isobutyl nitrite. The spasmolytic activity of the nitrite on isolated rabbit aortic strips was stronger, more rapid in onset, but less stable than the activity of the nitrate. In vitro tolerance to glyceryl trinitrate and isobutyl nitrite greatly weakened the activity of isobutyl nitrate, respectively, but had much less effect on isobutyl nitrite. Possible reasons for these differences are discussed.

Animals↗
PubMed1978

Intravenous fat tolerance in obese Africans with varying grades of carbohydrate tolerance.

An intravenous fat tolerance test (IVFTT) was performed and fasting plasma lipid values determined in 12 healthy normal weight, 18 obese non-diabetic, 9 obese chemical diabetic and 10 obese symptomatic diabetic African subjects. Their insulin responses to an oral glucose load were also determined. Mean plasma triglyceride levels were similar in the normal weight and obese non-diabetic groups but were significantly raised in the two diabetic groups, being highest in the symptomatic diabetics. The fractional removal-rate of an intravenous injection of the fat emulsion Intralipid was significantly less in each of the obese diabetic groups compared with the normal weight or obese non-diabetic group. There was a significant negative correlation in all but the symptomatic diabetic group between the fasting triglyceride level and the rate constants for the IVFTT. These results suggest that the rate of triglyceride clearance is an important determinant of the basal plasma triglyceride concentration in urban African subjects.

Adult↗
PubMed1984

Further evidence for a bidirectional effect of naloxone on the pain threshold in tolerant and non-tolerant arthritic rats.

In arthritic rats, low doses of naloxone induced powerful analgesic effects (as gauged by the vocalization threshold elicited by pressure on the paw) which were marked for 3 and 6 micrograms/kg IV, whereas high doses (1000 and 3000 micrograms/kg IV) induced hyperalgesia. This bidirectional effect persisted in arthritic rats rendered tolerant to morphine, but whereas the analgesic effects were suppressed or reduced, the hyperalgesic effects induced by the higher doses were unchanged. These results suggest that the analgesic and hyperalgesic effects might be mediated by different systems.

Animals↗
PubMed1988

Detection of immunological tolerance to bovine spumavirus (BSV) with evidence for salivary excretion and spread of BSV from the tolerant animal.

A group of 17 Friesian-Holstein steers held in individual pens was examined for evidence of infection with bovine spumavirus (BSV). Serum was examined for specific antibody by 2 serological procedures, and circulatory leucocytes and throat swabs were examined for the presence of circulatory leucocyte-associated BSV (CLAB) and saliva-associated BSV (SAB). Initial tests showed that 7 of the 17 steers had specific antibody to BSV by both serological procedures, and a further steer developed such antibody during the first 3 months of holding the animals in single contiguous pens. All 8 of these specific antibody-positive steers were CLAB positive and SAB negative. Nine steers showed no specific antibody to BSV by either of the 2 serological procedures; 8 of these 9 steers showed no evidence of CLAB or SAB. The exception was one steer which was CLAB- and SAB-positive at each of 30 samplings taken over a period of 9 months observation, whilst remaining specific-antibody free. This steer was classed as immunologically tolerant of BSV, and epidemiological data suggested that lateral spread of infection had originated from this animal through the agency of saliva.

Animals↗
PubMed2001

Tolerance and near-tolerance strategies in monkeys and their application to human renal transplantation.

Studies in non-human primates to evaluate tolerance strategies in organ transplantation have led to innovation in human transplantation. The two strategies we have studied in detail in non-human primates are T-cell depletion by anti-CD3 immunotoxin and co-stimulation blockade. Each of these strategies has been extended into early human trials in renal transplantation. The results of these human and non-human primate studies are summarized. Continued progress in better and safer immunosuppressive methods remains closely linked to research using non-human primates. However, there has not been a one-to-one correspondence between efficacy in the primate and efficacy in humans. Rather, principles can be derived from non-human primate studies that can be extended into human trials with the knowledge that regimens will likely differ in humans compared to non-human primates.

Animals↗
PubMed1974

Immunological tolerance in bone marrow-derived lymphocytes. 3. Tolerance induction in primed B cells by hapten conjugates of unrelated immunogenic or "nonimmunogenic" carriers.

The present studies were designed to probe the role(s) of T cells in preventing or altering tolerance induction in hapten-specific B cells. This was accomplished by using hapten conjugates of normally immunogenic heterologous carriers to selectively inhibit 2,4-dinitrophenyl (DNP)-primed B cells in adoptive transfer experiments in vivo. The data provide strong indications that one critical role of T-cell participation in humoral responses to antigens is to circumvent the development of a tolerogenic signal that, in the absence of such T-cell function, might otherwise ensue after binding of the antigenic determinants by specific precursor B lymphocytes.

Animals↗
PubMed1987

Self tolerance and localized autoimmunity. Mouse models of autoimmune disease that suggest tissue-specific suppressor T cells are involved in self tolerance.

Autoimmune diseases appeared frequently in adults in the prostate and stomach of C3.129 mice after thymectomy on day 3 (Tx-3) without any additional treatment. Lesions of both organs could be completely prevented by a single i.p. injection of spleen cells from syngeneic adult mouse on day 4. For prevention of prostatis, the most effective cell source was normal males (4 X 10(6); normal females or Orx-0 males were less effective as the cell source, and higher doses of cells (4 X 10(7)) were needed. In contrast, spleen cells (4 X 10(6)) from these three donors had equivalent capacity for the prevention of gastritis. Similar autoimmune prostatis developed at very high frequency when spleen cells (4 X 10(6)) from normal females or Orx-0 males, but not from normal males, were injected i.p. into C3.129 nu/nu mice at 4 d. However, no sign of prostatis was found in nu/+ recipients. Injection of a larger dose (4 X 10(7)) from the same donors was not effective for induction of prostatis. Gastritis could not be induced in nu/nu mice by this procedure. Injection of spleen cells from Tx-3 males or females was effective for induction of both prostatis and gastritis in nu/nu recipients. It was also shown that a T cell population (Thy-1.2+, Ig-) had the capacity to prevent and to induce autoimmune diseases. These results together strongly suggest a role for active tissue-specific suppressor T cells in self tolerance, and elimination of such T cell populations causes autoimmunity.

Animals↗
PubMed1982

Suppressor cells in transplantation tolerance. III. The role of antigen in the maintenance of transplantation tolerance.

Suppressor cells, which in an alloantigen-specific manner inhibit proliferation of donor cells to host antigens in a mixed lymphocyte culture and adoptively transfer the suppression of graft-versus-host disease (GVHD), undergo a gradual clonal reduction in long-term, allogeneic, histoincompatible rat radiation chimeras until they can no longer be measured in an in vitro suppressor cell assay. When lymphohematopoietic cells from these chimeras are transferred into lethally irradiated secondary recipients of original donor strain, the suppressor cells, now in a target antigen-free environment, undergo a further clonal reduction. After "parking" for 120 days, the chimeric cells are specifically tolerant to original host antigens, but cannot adoptively transfer suppression of GVHD. When chimeric cells, parked for 120 days in secondary recipients of original donor strain, are stimulated with original host-type antigen repeatedly during or once at the end of the parking period, the suppressor cell clone is expanded, suppressor cells can be identified in vitro, and suppression of GVHD can adoptively be transferred to tertiary recipients.

Animals↗
PubMed1986

Induction of transplantation tolerance in rats by spleen allografts. I. Evidence that rats tolerant of spleen allografts contain two phenotypically distinct T suppressor cells.

We have examined suppressor cell activity in transplantation tolerant (TT) rats bearing vascularized spleen allografts in several different donor-recipient combinations. More than 60% of WAG (RT-1u) and 65% of AGUS (RT-1l) spleen allografts were permanently accepted when transplanted to AGUS and PVG (RT-1c) rats, respectively. All (WAG X AGUS)F1 to AGUS and (AGUS X PVG)F1 to PVG spleen allografts survived indefinitely. Unseparated LNC, TDL, and whole T cell or W3/25+, OX8- T cell populations obtained from AGUS rats bearing (WAG X AGUS)F1 spleens exhibited reduced mixed lymphocyte reaction (MLR) responses to the spleen donor, and to some extent to BN(RT1n) third-party stimulators, but responded normally to PVG.A(RT1a) stimulators. Coculture experiments demonstrated that lymph node cells (LNC) and thoracic duct lymphocytes (TDL) of TT rats contain RT1 specific suppressor cells. Furthermore, T cells isolated from all donor-recipient combinations contained two phenotypically distinct suppressor cell populations: a radiosensitive W3/25+, OX8- (Th/i) and a relatively radioresistant W3/25-, OX8+ (Ts/c). These Ts may be responsible for the maintenance of TT.

Animals↗
PubMed1979

The use of hapten-polysaccharide conjugates for the induction of B-cell tolerance involving IgE responses. III. Specific tolerance induced by sulphonamide-substituted levan in the guinea pig.

Inbred strain 2 and (strain 2 x strain 13)F1 guinea pigs were made allergic by intraperitoneal injections of sulphonamide-chicken gamma-globulin (CGG) conjugates. Two sulphonamides were used: 4-sulphanilamide benzoic acid (4-SABA) and sulphamethoxazole (SMX). 4-SABA was coupled to CGG through its carboxylic group and SMX was coupled following diazotization of its sulphanilamide group. The anti-4-SABA and anti-SMX reaginic antibodies formed did not show any cross-reactivity with each other. Injection of 4-SABA coupled to native levan effectively suppressed the allergic responses of these guinea pigs when given either prior to or after immunization with 4-SABA-CGG. This treatment is specific as it did not affect anti-SMX or anti-CGG reaginic responses. Guinea pigs seem more sensitive to the regime used for tolerance induction than correspondingly sensitized mice in that less tolerogen is required on a body weight basis.

Animals↗
PubMed1984

Kinetics of oral tolerance: study of variables affecting tolerance induced by oral administration of antigen.

The induction of antigen-specific tolerance by oral administration of hen egg albumin (OVA) was shown to be time- and dose-dependent. The IgE response was the most effectively suppressed by antigen feeding prior to or after parenteral immunization. The effect on IgG response paralleled that observed on the IgE response, but the magnitude of suppression was less pronounced. The IgA response was enhanced rather than suppressed if the interval between feeding and parenteral immunization was short or if the animals were antigen-fed after the intraperitoneal priming.

Administration, Oral↗
PubMed1983

Tolerance and cross-tolerance to morphine and ethanol in mice selectively bred for differential sensitivity to ethanol.

Ethanol-sensitive long-sleep mice showed greater sensitivity to ethanol-induced hypothermia whereas the less sensitive short-sleep mice showed greater sensitivity to morphine-induced hypothermia. The short-sleep mice, but not the long-sleep mice, displayed a degree of cross-tolerance to the hypothermic effects of ethanol following repeated exposure to morphine.

Animals↗
PubMed2006

Comparison between 100-g glucose tolerance test and two other screening tests for gestational diabetes: combined fasting glucose with risk factors and 50-g glucose tolerance test.

CONTEXT AND OBJECTIVE: Lack of consensus about which screening tests to use for gestational diabetes mellitus (GDM) and difficulties in performing the gold-standard diagnostic test, the 100-g glucose tolerance test (100-g GTT), justify comparison with alternatives. The aim was to compare this with two other screening tests: combined fasting glucose with risk factors (FG + RF) and 50-g GTT. DESIGN AND SETTING: Prospective longitudinal cohort study in the Hospital School of Universidade Federal de Mato Grosso do Sul. METHODS: The three tests were performed independently on 341 pregnant women. Sensitivity (S), specificity (Sp), positive (PPV) and negative (NPV) predictive values, positive (PLR) and negative (NLR) likelihood ratios, and false-positive (FP) and false-negative (FR) rates obtained with FG + RF and 50-g GTT were compared with values from 100-g GTT. The average one-hour post-intake glucose levels (1hPG) with 50-g and 100-g were compared. Students t test was used in the statistical analysis. RESULTS: FG + RF led more pregnant women (53.9%) to diagnostic confirmation than did 50-g GTT (14.4%). The tests were equivalent for S (86.4 and 76.9%), PPV (98.7 and 98.9%), NLR (0.3 and 0.27) and FR (15.4 and 23.1%). Average 1hPG values were similar: 50-g GTT = 106.8 mg/dl and 100-g GTT = 107.5 mg/dl. CONCLUSION: Diagnostic efficiency with simplicity, practicality and low cost make FG + RF more appropriate for screening for GDM. The equivalence of 1hPG allows a new, cheaper and less uncomfortable protocol to be proposed for screening and diagnosing GDM.

Adult↗