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PubMed1996

Antioxidant Response to NaCl Stress in a Control and an NaCl-Tolerant Cotton Cell Line Grown in the Presence of Paraquat, Buthionine Sulfoximine, and Exogenous Glutathione.

A cotton (Gossypium hirsutum L.) control and NaCl-tolerant cell line (cv Coker 312) were grown on media with or without NaCl in the presence or absence of paraquat, buthionine sulfoximine, and oxidized glutathione. On medium with 150 mM NaCl the NaCl-tolerant cell line exhibited no reduction in growth, whereas a 96% reduction was observed in the control line. The NaCl-tolerant cell line that was grown on 150 mM NaCl exhibited significantly greater catalase (341%), peroxidase (319%), glutathione reductase (287%), ascorbate peroxidase (450%), [gamma]-glutamylcysteine synthetase (224%), and glutathione S-transferase (500%) activities than the intolerant control. The NaCl-tolerant cell line had a significantly lower dehydroascorbic acid/ascorbic acid ratio. Paraquat reduced growth by 20 and 53.7%, respectively, in the NaCl-tolerant and control cell line. The NaCl-tolerant cell line also showed a slight tolerance to buthionine sulfoximine. In the buthionine sulfoximine experiments reduced glutathione restored growth in both cell lines, whereas oxidized glutathione restored growth only in the NaCl-tolerant cell line. These data indicate that the NaCl-tolerant cell line exhibited a cross-tolerance to a variety of stress variables and had a more active ascorbate-glutathione cycle.

Journal Article↗
PubMed1999

Water content, raffinose, and dehydrins in the induction of desiccation tolerance in immature wheat embryos

Desiccation tolerance is initiated in wheat (Triticum aestivum L.) embryos in planta at 22 to 24 d after anthesis, at the time that the embryo water content has decreased from about 73% fresh weight (2.7 g water/g dry weight) to about 65% fresh weight (1.8 g water/g dry weight). To determine if desiccation tolerance is fully induced by the loss of a relatively small amount of water, detached wheat grains were treated to reduce the embryo water content by just a small amount to approximately 69% (2.2 g water/g dry weight). After 24 h of such incipient water loss, subsequently excised embryos were able to withstand severe desiccation, whereas those embryos that had not previously lost water could not. Therefore, a relatively small decrease in water content for only 24 h acts as the signal for the development of desiccation tolerance. Embryos that were induced into tolerance by a 24-h water loss had no detectable raffinose. The oligosaccharide accumulated at later times even in embryos of detached grains that had not become desiccation tolerant, although tolerant embryos (i.e. those that previously had lost some water) contained larger amounts of the carbohydrate. It is concluded that desiccation tolerance and the occurrence of raffinose are not correlated. Immunodetected dehydrins accumulated in embryos in planta as desiccation tolerance developed. Detachment of grains induced the appearance of dehydrins at an earlier age, even in embryos that had not been made desiccation tolerant by incipient drying. It is concluded that a small reduction in water content induces desiccation tolerance by initiating changes in which dehydrins might participate but not by their interaction with raffinose.

Journal Article↗
PubMed1984

Heat Stress Responses in Cultured Plant Cells : Heat Tolerance Induced by Heat Shock versus Elevated Growing Temperature.

Using cultured pear (Pyrus communis cv Bartlett) cells, heat tolerance induced by heat shock was compared to that developed during growth at high temperature. After growth at 22 degrees C, cells exposed to 38 degrees C for 20 minutes (heat shock) showed maximum increased tolerance within 6 hours. Cells grown at 30 degrees C developed maximum heat tolerance after 5 to 6 days; this maximum was well below that induced by heat shock. Heat shock-induced tolerance was fully retained at 22 degrees C for 2 days and was only partly lost after 4 days. However, pear cells acclimated at 30 degrees C lost all acquired heat tolerance 1 to 2 days after transfer to 22 degrees C. In addition, cells which had been heat-acclimated by growth at 30 degrees C showed an additional increase in heat tolerance in response to 39 degrees C heat shock. The most striking difference between heat shock and high growth temperature effects on heat tolerance was revealed when tolerance was determined using viability tests based on different cell functions. Growth at 30 degrees C produced a general hardening, i.e. increased heat tolerance was observed with all three viability tests. In contrast, significantly increased tolerance of heat-shocked cells was observed only with the culture regrowth test. The two types of treatment evoke different mechanisms of heat acclimation.

Journal Article↗
PubMed2004

Costs and benefits of cold tolerance in transgenic Arabidopsis thaliana.

Cold tolerance in plants is an ecologically important trait that has been under intensive study for basic and applied reasons. Determining the fitness benefits and costs of cold tolerance has previously been difficult because cold tolerance is normally an induced trait that is not expressed in warm environments. The recent creation of transgenic plants constitutively expressing cold tolerance genes enables the investigation of the fitness consequences of cold tolerance in multiple temperature environments. We studied three genes from the CBF (C-repeat/dehydration responsive element binding factor) cold tolerance pathway, CBF1, 2 and 3, in Arabidopsis thaliana to test for benefits and costs of constitutive cold tolerance. We used multiple insertion lines for each transgene and grew the lines in cold and control conditions. Costs of cold tolerance, as determined by fruit number, varied by individual transgene. CBF2 and 3 overexpressers showed costs of cold tolerance, and no fitness benefits, in both environments. CBF1 overexpressing plants showed no fitness cost of cold tolerance in the control environment and showed a marginal fitness benefit in the cold environment. These results suggest that constitutive expression of traits that are normally induced in response to environmental stress will not always lead to costs in the absence of that stress, and that the ecological risks of CBF transgene escape should be assessed prior to their use in commercial agriculture.

Adaptation, Physiological↗
PubMed1996

Role of nitric oxide in the induction and expression of morphine tolerance and dependence in mice.

1. The possible involvement of nitric oxide (NO) in the induction and expression of morphine tolerance and dependence was studied in mice. A two-day repeated injection regimen was used to induce morphine tolerance and dependence. Tolerance was assessed by the tail flick test and physical dependence by naloxone challenge, on the third day. 2. Two days pretreatment with L-arginine (20 mg kg-1, twice daily) or D-NG-nitro arginine methyl ester (D-NAME, 20 mg kg-1, twice daily) alone had no effect on subsequent morphine antinociception. L-NG-monomethyl arginine (L-NMMA, 10 mg kg-1, twice daily) for two days led to a slight increase (not statistically significant) in morphine antinociception; while L-NG-nitro arginine methyl ester (L-NAME, 10 mg kg-1, twice daily) for two days led to attenuation of morphine analgesia. None of the animals treated with these drugs alone showed signs characteristic of the opioid withdrawal syndrome upon naloxone challenge. 3. Induction phase L-arginine slowed the development of opioid tolerance and physical dependence, while L-NAME and L-NMMA led to a higher degree of tolerance but had no effect on the development of physical dependence. 4. L-Arginine and D-NAME had no effect on the expression of morphine tolerance and physical dependence. Expression phase L-NAME and L-NMMA, on the other hand, attenuated morphine tolerance and reduced the incidence of withdrawal signs. 5. NO may, therefore, play a role in both phases of morphine tolerance and dependence: elevation of NO levels during the induction phase delays the development of opioid tolerance/dependence, while inhibition of NO synthase accelerates the development of tolerance. Inhibition of NO attenuates the expression of both tolerance and physical dependence.

Animals↗
PubMed1994

Role of tolerance in treatment and prophylaxis of experimental Staphylococcus aureus endocarditis with vancomycin, teicoplanin, and daptomycin.

The role of Staphylococcus aureus tolerance in the treatment and prophylaxis of endocarditis in rats was investigated. The efficacies of vancomycin, teicoplanin, and daptomycin, alone and in combination with rifampin, were compared in rats with endocarditis infected with a tolerant strain of S. aureus and in rats with endocarditis infected with its nontolerant variant. In vitro the cloxacillin-tolerant strain was also tolerant to vancomycin and teicoplanin, but not to daptomycin. However, tolerance to these antibiotics did not influence the results of treatment of experimental S. aureus endocarditis. There was no difference in the bacterial densities in the vegetations of rats infected with either the tolerant or the nontolerant strain after 5 days of treatment with any of the antibiotic regimens. Of all antibiotics, daptomycin was the most effective in reducing bacterial numbers in vegetations. Combination of rifampin with vancomycin or teicoplanin improved the results of treatment for the tolerant as well as the nontolerant strains. Daptomycin was as effective alone as in combination with rifampin. In contrast, tolerance influenced the prophylactic effects of vancomycin and teicoplanin. The proportion of rats with sterile vegetations after prophylaxis with vancomycin or teicoplanin at a low dose was lower for those infected with the tolerant strain than for those infected with the nontolerant strain. A low dose of daptomycin was equally effective against the tolerant and the nontolerant strains. However, higher doses of all three antibiotics afforded almost full protection against both strains.

Animals↗
PubMed2000

Deregulation of the arginine deiminase (arc) operon in penicillin-tolerant mutants of Streptococcus gordonii.

Penicillin tolerance is an incompletely understood phenomenon that allows bacteria to resist drug-induced killing. Tolerance was studied with independent Streptococcus gordonii mutants generated by cyclic exposure to 500 times the MIC of penicillin. Parent cultures lost 4 to 5 log(10) CFU/ml of viable counts/24 h. In contrast, each of four independent mutant cultures lost < or =2 log(10) CFU/ml/24 h. The mutants had unchanged penicillin-binding proteins but contained increased amounts of two proteins with respective masses of ca. 50 and 45 kDa. One mutant (Tol1) was further characterized. The two proteins showing increased levels were homologous to the arginine deiminase and ornithine carbamoyl transferase of other gram-positive bacteria and were encoded by an operon that was >80% similar to the arginine-deiminase (arc) operon of these organisms. Partial nucleotide sequencing and insertion inactivation of the S. gordonii arc locus indicated that tolerance was not a direct consequence of arc alteration. On the other hand, genetic transformation of tolerance by Tol1 DNA always conferred arc deregulation. In nontolerant recipients, arc was repressed during exponential growth and up-regulated during postexponential growth. In tolerant transformants, arc was constitutively expressed. Tol1 DNA transformed tolerance at the same rate as transformation of a point mutation (10(-2) to 10(-3)). The tolerance mutation mapped on a specific chromosomal fragment but was physically distant from arc. Importantly, arc deregulation was observed in most (6 of 10) of additional independent penicillin-tolerant mutants. Thus, although not exclusive, the association between arc deregulation and tolerance was not fortuitous. Since penicillin selection mimicked the antibiotic pressure operating in the clinical environment, arc deregulation might be an important correlate of naturally occurring tolerance and help in understanding the mechanism(s) underlying this clinically problematic phenotype.

Amino Acids↗
PubMed1968

Differential tolerance of streptomycetes to sodium chloride as a taxonomic aid.

A survey was made of the NaCl tolerance of approximately 1,300 Streptomyces strains belonging to 313 species. The growth medium of the organisms was supplemented with a graded series of NaCl concentrations (4, 7, 10, and 13%). Only 1.8% of the species could not tolerate 4% NaCl; 26.9% could grow at a maximum of 4%; 49.7% could tolerate a maximum of 7%; 18.8% could grow at a maximum of 10%; and only 2.8% could tolerate 13% NaCl. In evaluating the relationships of NaCl tolerance to various taxonomic features, higher tolerance was statistically associated with the "yellow" and possibly the "white"-spored streptomycetes, whereas the "red"-spored series tended to have lesser tolerance. Higher tolerance was also indicated for spiny-spored species, as a group, than for smooth-spored forms. Likewise, nonproducers of melanin, collectively, were more NaCl tolerant than melanin-producing species. Uniformity of test responses between strains of species studied suggested the usefulness of NaCl tolerance as a taxonomic criterion.

Culture Media↗
PubMed2005

Cadmium tolerance plasticity in Rhizobium leguminosarum bv. viciae: glutathione as a detoxifying agent.

Rhizobium leguminosarum bv. viciae strains expressing different degrees of tolerance to metal stress were used in this work to study the basic mechanisms underlying heavy metal tolerance. We used various parameters to evaluate this response. The strains' growth responses under different Cd2+ concentrations were determined and we reported variation in Cd2+ tolerance. Total soluble protein content decreased drastically, revealing the toxic effects that intracellular Cd2+ imposes on cellular metabolism, but this decrease in protein content was particularly evident in sensitive and moderately tolerant strains. Tolerant strains presented the highest intracellular and wall-bound Cd2+ concentrations. Cd2+ induced increases in the expression of some specific proteins, which were identical in all tolerant strains. Glutathione levels remained unaltered in the sensitive strain and increased significantly in tolerant and moderately tolerant strains, suggesting the importance of glutathione in coping with metal stress. This work suggests that efflux mechanisms may not be the only system responsible for dealing with heavy metal tolerance. A clear correlation between glutathione levels and Cd2+ tolerance is reported, thus adding a novel aspect in bacteria protection against heavy metal deleterious effects.

Bacterial Proteins↗
PubMed2003

The Singapore impaired glucose tolerance follow-up study: does the ticking clock go backward as well as forward?

OBJECTIVE: To 1). document the change in glucose tolerance for subjects with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) over time, 2). identify baseline factors associated with worsening of glucose tolerance, and 3). determine whether cardiovascular disease (CVD) risk factors associated with IGT improved in tandem with glucose tolerance. RESEARCH DESIGN: Subjects with IGT and NGT (matched for age, sex, and ethnic group) were identified from a cross-sectional survey conducted in 1992. Subjects with IGT (297) and NGT (298) (65.0%) were reexamined in 2000. Glucose tolerance (assessed by 75-g oral glucose tolerance test), anthropometric data, serum lipids, blood pressure, and insulin resistance were determined at baseline and at the follow-up examination. RESULTS: For NGT subjects, 14.0% progressed to IGT and 4.3% to diabetes over 8 years. For IGT subjects, 41.4% reverted to NGT, 23.0% remained impaired glucose tolerant, and 35.1% developed diabetes. Obesity, hypertriglyceridemia, higher blood pressure, increased insulin resistance, and lower HDL cholesterol at baseline were associated with worsening of glucose tolerance in both IGT and NGT subjects. Those with IGT who reverted to NGT remained more obese and had higher blood pressure than those with NGT in both 1992 and 2000. However, serum triglyceride, HDL cholesterol, and insulin resistance values in 2000 became indistinguishable from those of subjects who maintained NGT throughout the study period. CONCLUSIONS: Some, but not all, CVD risk factors associated with IGT and with the risk of future diabetes normalize when glucose tolerance normalizes. Continued surveillance and treatment in subjects with IGT, even after they revert to NGT, may be important in the prevention of CVD.

Adult↗
PubMed1975

+Gz tolerance in man after 14-day bedrest periods with isometric and isotonic exercise conditioning.

The purpose of this study was to determine the effects of isometric or isotonic exercise training on post-bedrest +Gz tolerance. Seven male volunteers, 19-22 years, underwent accelerations of +2.1 Gz (740 s), +3.2 Gz (327 s), and +3.8 Gz (312 s) in a selected, randomized order; the ramp to peak acceleration was 1.8 G/min. The centrifugation runs were terminated by loss of central vision (blackout) to a white light with a luminance of 3.15 times 10-5 log candle/cm-2 (0.092 ft-lambert). The study began with a 14-d ambulatory control period, followed by three 14-d bedrest periods (each separated by a 21-d recovery period) and then a final week of recovery. During the ambulatory periods, the subjects exercised on a bicycle ergometer at 50% of their maximal oxygen uptake (max VO2) for 1 h/d. During two of the three bedrest periods, the subjects performed in the supine position one of two routines, either isometric exercise (21% of max leg extension force for 1 min followed by 1-min rest) or isotonic exercise (68% of max VO2) for 0.5 in the morning and afternoon. During the third bedrest period, no exercise was performed. In general +Gz tolerance was reduced by 24% to 35% (p less than or equal to 0.05) after bedrest. Compared with control values, there were significant reductions in average tolerance times after bedrest with no exercise and isotonic exercise at all G levels. With isometric exercise, there was a significant decrease in tolerance at 2.1 Gz but not at 3.2 Gz or 3.8 Gz, even though the latter tolerances were reduced 15.6% and 10.0%, respectively. Both exercise regimens maintained tolerance at levels equal to or above that obtained with no exercise. Compared with control values, average tolerances were lower (p less than or equal to 0.05) after the two recovery periods between the bedrest periods (minus 24% to minus 26% at 3.2 Gz and 3.8 Gz), indicating that 3 weeks of ambulation was not sufficient time for full recovery from the deconditioning induced in this study. A prediction equation was constructed with data from all comparable studies utilizing deconditioned men riding relaxed without protective garments: Tolerance (in seconds) equals minus 334 + (1715/+Gz level). From this equation, the calculated tolerance after bedrest is 13.5 min at 1.5 G, and the point of zero tolerance is 5.1 Gz.

Acceleration↗
PubMed2004

Population variation in the cost and benefit of tolerance and resistance against herbivory in Datura stramonium.

In this study we examine the hypothesis that divergent natural selection produces genetic differentiation among populations in plant defensive strategies (tolerance and resistance) generating adaptive variation in defensive traits against herbivory. Controlled genetic material (paternal half-sib families) from two populations of the annual Datura stramonium genetically differentiated in tolerance and resistance to herbivory were used. This set of paternal half-sib families was planted at both sites of origin and the pattern of genotypic selection acting on tolerance and resistance was determined, as well as the presence and variation in the magnitude of allocational costs of tolerance. Selection analyses support the adaptive differentiation hypothesis. Tolerance was favored at the site with higher average level of tolerance, and resistance was favored at the site with higher average level of resistance. The presence of significant environmentally dependent costs of tolerance was in agreement with site variation in the adaptive value of tolerance. Our results support the expectation that environmentally dependent costs of plant defensive strategies can generate differences among populations in the evolutionary trajectory of defensive traits and promote the existence of a selection mosaic. The pattern of contrasting selection on tolerance suggests that, in some populations of D. stramonium, tolerance may alter the strength of reciprocal coevolution between plant resistance and natural enemies.

Adaptation, Biological↗
PubMedDate not supplied

Facial tolerability of topical retinoid therapy.

The facial tolerability of various topical retinoids was evaluated in 253 healthy volunteers in a series of split-face, randomized, investigator-masked studies-all conducted at the same site by the same investigator. Four variables were evaluated to determine if they influenced tolerability-retinoid concentration, formulation vehicle, skin sensitivity, and individual retinoid. Lower retinoid concentrations were associated with less irritation. Vehicle influenced tolerability but whether a gel or cream formulation was better tolerated varied from retinoid to retinoid. Tolerability was superior on normal skin than "sensitive skin." On normal skin, tazarotene cream was better tolerated than tretinoin cream whereas adapalene and tretinoin microsponge gels were better tolerated than tazarotene gel. On sensitive skin, tazarotene and adapalene creams were better tolerated than tretinoin cream whereas adapalene gel was better tolerated than tazarotene gel. Retinoid concentration, vehicle, skin sensitivity, and retinoid can all affect facial tolerability. Skin vulnerability may be the most important factor.

Adapalene↗
PubMed2006

The evolution of parasites in response to tolerance in their hosts: the good, the bad, and apparent commensalism.

Tolerance to parasites reduces the harm that infection causes the host (virulence). Here we investigate the evolution of parasites in response to host tolerance. We show that parasites may evolve either higher or lower within-host growth rates depending on the nature of the tolerance mechanism. If tolerance reduces virulence by a constant factor, the parasite is always selected to increase its growth rate. Alternatively, if tolerance reduces virulence in a nonlinear manner such that it is less effective at reducing the damage caused by higher growth rates, this may select for faster or slower replicating parasites. If the host is able to completely tolerate pathogen damage up to a certain replication rate, this may result in apparent commensalism, whereby infection causes no apparent virulence but the original evolution of tolerance has been costly. Tolerance tends to increase disease prevalence and may therefore lead to more, rather than less, disease-induced mortality. If the parasite is selected, even a highly efficient tolerance mechanism may result in more individuals in total dying from disease. However, the evolution of tolerance often, although not always, reduces the individual risk of dying from infection.

Animals↗
PubMed1996

Induction of humoral immune tolerance to major histocompatibility complex antigens by transfusions of UVB-irradiated leukocytes.

To determine whether immune tolerance to donor major histocompatibility complex (MHC) antigens can be induced by transfusions of UVB-irradiated leukocytes, studies were conducted in inbred strains of mice with well-characterized MHC antigens. CBA mice with H-2k phenotype and BALB/c mice with H-2d phenotype were used as recipients and donors, respectively. Humoral immune tolerance is defined as absence of antibody response after challenge with transfusions of untreated donor leukocytes. It was found that transfusions of purified peripheral blood mononuclear leukocytes irradiated with 1,200 mJ/cm2 UVB not only prevented allo-immunization but also induced humoral immune tolerance to donor class-I and -II MHC antigens in all recipient mice. Donor plasma and platelets interfered with the induction of this tolerance. The tolerance induction by UVB-irradiated leukocytes is dose-dependent. Four weekly transfusions of 2 x 10(5) leukocytes were required to ensure tolerance induction in all mice. The results of a long-term follow-up study showed that the induced tolerance is long-lasting and can withstand repeated challenges by untreated donor leukocytes. Recipient mice tolerant to H-2d antigens also became tolerant to H-2b, H-2r, and H-2n MHC antigens but did not have impaired antibody responses to antigens unrelated to donor leukocytes. Adoptive transfer experiments showed the development of negative regulatory cells in spleens of the tolerized mice. In view of recent feasibility of using UVB-irradiated human platelet concentrates for prevention of HLA alloimmunization, the findings of this study support that UVB-irradiated donor leukocytes could have potential, important clinical application in transplantation medicine.

Adoptive Transfer↗
PubMed2026

Integrated multi-omics analysis of fluoroquinolone tolerance mechanisms induced by enrofloxacin in Pasteurella multocida.

BACKGROUND: The global prevalence of multidrug-resistant bacteria has been rising at an alarming rate, posing a serious threat to both human and animal health. However, the mechanisms by which bacteria acquire antibiotic tolerance and subsequently develop resistance remain incompletely understood. METHODS: In this study, Pasteurella multocida, a common pathogen in the animal husbandry industry, was exposed to enrofloxacin, and genome resequencing, transcriptomic, and metabolomic analyses were performed to elucidate the adaptive mechanisms of P. multocida under fluoroquinolone-induced stress. RESULTS: Compared with the wild-type strain, the enrofloxacin-tolerant strain exhibited an extended lag phase, a prolonged logarithmic phase, reduced sensitivity to polymyxin B, reduced biofilm formation, and an elongated cellular morphology. Multi-omics analysis revealed a deletion in the dusB gene of the tolerant strain, resulting in a truncated non-functional protein. The deletion of dusB enhanced tolerance by prolonging the lag phase and reducing the growth rate. Moreover, the expression of genes in the CAMP pathway was up-regulated, and deletion of cpxR further promoted tolerance by modulating ribosome-associated genes. Integrated transcriptomic and metabolomic analyses indicated activation of the tricarboxylic acid (TCA) cycle during tolerance development. CONCLUSION: This study identified dusB and cpxR as key genes mediating enrofloxacin tolerance in P. multocida, elucidated the association between the antibiotic tolerance, growth, and gene expression, and may provide potential targets for future strategies aimed at limiting tolerance-associated resistance development.

Enrofloxacin↗
PubMed1980

Effects of tolerance on the anxiety-reducing function of alcohol.

Thirty-two male social drinkers were arranged into two tolerance groups, based on changes in standing stability after ingestion of alcohol. Subjects consumed either a large (1.0 g/kg) or small (0.5 g/kg) dose of alcohol. On finishing their drinks, subjects were requested to interact with a female confederate whose continued silence induced anxiety. Heart rate, skin conductance, overt behavior, and self-report measures were taken. Heart rate increased more at the small than the large dose, consistent with the tension-reduction hypothesis. Further, heart rate of high-tolerance subjects increased significantly more than that of low-tolerance subjects, which suggests that alcohol was less effective at tension reduction for the high-tolerance group. Finally, measures of both skin conductance and heart rate showed significant dose-by-tolerance interactions. High-tolerance subjects were more aroused than were low-tolerance subjects at the small but not at the large dose, suggesting that high-tolerance subjects must consume more alcohol to achieve the same autonomic effect experienced by the low-tolerance subjects.

Adolescent↗
PubMed1996

Neonatal injection of Lewis rats with recombinant V beta 8.2 induces T cell but not B cell tolerance and increased severity of experimental autoimmune encephalomyelitis.

In Lewis rats with experimental autoimmune encephalomyelitis (EAE) mediated by V beta 8.2 effector cells, anti-idiotypic T cells and antibodies could be boosted by injection of V beta 8.2 peptides, inducing both T cells and antibodies that reduced the severity and shortened the course of disease. However, EAE in Lewis rats is self-limiting, and we sought to determine if the anti-idiotypic response contributed to the natural recovery process. In a previous study, we found that adult tolerance induced to one of the regulatory idiotopes, V beta 8.2-44-54, caused worsening of EAE, implicating response to this epitope in recovery from EAE. However, neonatally-induced tolerance to V beta 8.2-44-54 did not alter the course of EAE, suggesting either compensation by additional V beta 8.2 determinants, or mechanistic differences in tolerization protocols. In this report, we reevaluate the role of V beta 8.2 determinants in recovery from EAE, using two recombinant V beta 8.2 constructs to induce neonatal tolerance to the comprehensive set of V beta 8.2 epitopes prior to adult induction of EAE. We found that neonatal exposure to either of the recombinant V beta 8.2 molecules induced "split" tolerance-specific T cell tolerance but enhanced antibody responses- and a more severe course of EAE. In contrast, neonatal exposure to a V beta 8.2 + T cell hybridoma or a control protein did not induce T cell tolerance to V beta 8.2 determinants and did not alter the EAE disease course. These results are consistent with those obtained by inducing adult tolerance, and suggest that our previous result (normal recovery from EAE in rats neonatally tolerized to V beta 8.2-44-54) was probably due to a compensatory response to other V beta 8.2 determinants. In both studies, the data clearly implicate T cell recognition of V beta 8.2 determinants in the natural EAE recovery process.

Amino Acid Sequence↗