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At least 343 records · Page 19Linked to original sources

PubMed2000

Naked DNA vaccination differentially modulates autoimmune responses in experimental autoimmune encephalomyelitis.

Vaccination with naked DNA represents a therapeutic strategy currently under consideration in multiple sclerosis (MS). In this study, we tested the potential therapeutic effect of vaccination with a naked DNA construct encoding proteolipid protein (pRc/CMV-PLP) upon the outcome of subsequent sensitization for experimental autoimmune encephalomyelitis (EAE) actively-induced in SJL mice with PLP139-151 peptide in adjuvant. Intramuscular vaccination with the naked DNA pRc/CMV-PLP construct led to PLP expression in local muscle tissue that persisted for about 8 weeks. Early sensitization for EAE (4 weeks after DNA vaccination) caused recipient mice to develop a severe, exacerbated form of disease (in comparison to control mice), while late sensitization (>10 weeks) resulted in a milder, ameliorated form. In the groups sensitized <10 weeks post-DNA vaccination with pRc/CMV-PLP induction of a Th1-type cytokine response was noted. In contrast, sensitization >10 weeks post-DNA vaccination led to peripheral tolerance as evidenced by a decrease in T cell proliferation and cytotoxic T cell response, no Th2 response, and no increase in apoptosis. These data are novel in that they demonstrate a differential effect of DNA vaccination and have important implications for its use as a mechanism to enhance or modulate immune reactivity.

Animals↗

PubMed2001

Experimental autoimmune uveoretinitis in mice (Biozzi ABH and NOD) expressing the autoimmune-associated H-2A(g7) molecule: identification of a uveitogenic epitope.

To determine whether Biozzi ABH (H-2A(g7)) mice were susceptible to chronic experimental autoimmune uveoretinitis (EAU). Biozzi ABH were immunized with the two retinal antigens, interphotoreceptor retinoid binding protein (IRBP) and soluble antigen (S-Ag). Biozzi ABH mice were found to be susceptible to EAU induction with native bovine IRBP. Recombinant protein domains were used to identify IRBP domain 2 (EcR2) as the uveitogenic domain. Histopathological examination indicated that EcR2-induced disease was of a chronic, non-destructive nature in the Biozzi ABH. Using synthetic overlapping peptides corresponding to EcR2, a uveitogenic and immunogenic epitope was identified corresponding to human IRBP511-530. Non-obese diabetic (NOD) mice share the same MHC class II (H-2A(g7)) molecule as the Biozzi ABH, and were also found to be susceptible to EAU induction with EcR2. This study has identified a novel mouse model of EAU, whereby disease is of a chronic, non-destructive nature, which has potential to be used in immune manipulation and neuroprotection studies.

Animals↗

PubMed1997

Present status of autoimmune hepatitis in Japan--correlating the characteristics with international criteria in an area with a high rate of HCV infection. Japanese National Study Group of Autoimmune Hepatitis.

BACKGROUND/AIMS: A nationwide survey of autoimmune hepatitis (AIH) was carried out in Japan. METHODS: Four hundred and ninety-six patients were enrolled by questionnaires sent to 101 hospitals with hepatology specialists. RESULTS: The clinical features of Japanese AIH were as follows: most patients were middle-aged women; serum autoantibodies, especially antinuclear antibody, were frequently positive, serum IgG level was high, and HLA-DR4 was the major HLA allotype. Liver-kidney microsomal type 1 antibody was positive in nine of 79 patients tested. Eight of these antibody positive patients were also positive for antinuclear antibody and five for anti-smooth muscle antibody. Ninety-two percent of the patients showed piecemeal necrosis and 60% bridging necrosis; plasma cell infiltration in the portal areas was observed in 50% of the patients. Only 12.3% were diagnosed as having liver cirrhosis. A favorable effect of corticosteroid, normalization of serum transaminases, was observed in 89% of 317 patients, who were treated with an initial dose of over 30 mg/day. Sixty-two patients were positive for hepatitis C virus (HCV) markers. In these patients, however, only one patient was liver-kidney microsomal type 1 antibody positive. Corticosteroid was effective in 30 (81%) of 37 HCV-marker-positive patients treated with this agent. Thus the efficacy of corticosteroid did not differ from that in AIH patients without HCV infection (90%). Similarly, interferon treatment was used in 20 patients, all of whom were positive for HCV-RNA, and resulted in 50% efficacy as determined by normalization of the serum transaminase level 6 months after treatment. The International Diagnostic Scoring System for the diagnosis of AIH worked well in these patients, except for HCV-infected individuals, that is, approximately 10% of the total of AIH patients.

Adolescent↗

PubMed1986

Increased amplifier T cell activity in autoimmune NZB mice and its possible significance in the expression of autoimmune disease.

The expression of amplifier- and helper-T cell activity was examined in NZB/N mice of different ages. Amplifier T cell activity develops in a cyclic manner; it decreases between 16 and 35 wk of age and then increases to maximal levels in mice older than 50 wk of age. The loss of suppressor T cell activity and increased amplifier T cell activity coincide with the development of autoimmune diseases in aging NZB/N mice. Although helper T cell activity is evident in young NZB/N mice, it is absent in old NZB/N mice expressing maximal amplifier T cell activity. This provides additional support for the fact that amplifier and helper functions are mediated by different subpopulations of T cells.

Age Factors↗

PubMedDate not supplied

[Cyclosporin and autoimmune diseases. 2: Human autoimmune diseases].

The effectiveness of cyclosporin against human auto-immune diseases has been well established in uveitis, rheumatoid arthritis and insulin-dependent diabetes. No firm conclusion can be drawn from trials conducted in other diseases, since the results are discordant or based on an insufficient number of subjects. In view of the side-effects, and notably the risk of nephrotoxicity, of the drug, the blood levels of cyclosporine must be measured and the patient's renal function evaluated at regular intervals. For the time being, these risks reduce the prescription of cyclosporin to the severe forms of autoimmune diseases, i.e. those which resist conventional corticosteroid therapy. Things are different with diabetes, since cyclosporin is the only immunosuppressant which has proved effective in inducing remissions. But whether such remissions can be maintained in the long term remains uncertain, and this type of treatment is still limited to therapeutic trials.

Autoimmune Diseases↗

PubMed1995

[Autoimmune hepatitis, autoimmune gastritis, hypergastrinemia and stomach carcinoid].

A 48-year-old woman with type II diabetes developed fatigue, arthralgia and myalgia. A few weeks later she was found to have hepatomegaly. The erythrocyte sedimentation rate was raised (53/93 mm), as were liver enzyme activities (GOT 186 U/l; GPT 240 U/l; gamma-GT 199 U/l), the gamma-globulin levels (40.7%;IgG 4470 mg/dl, IgA 698 mg/dl, IgM 245 mg/dl), antinuclear antibodies and antibodies against double-strand DNA, smooth muscles and actin. Laparoscopy revealed small-nodular liver cirrhosis. The autoimmune hepatitis was treated with prednisolone (initially 60 mg daily, then reduced to 10 mg daily) and azathioprine (initially 100 mg daily, reduced to 50 mg daily). The symptoms markedly improved. But one year later, during follow-up examination, gastric polyps were found, excised and histologically found to be carcinoid. The gastrin level was raised to 765 pg/ml. Another year later the liver cirrhosis had advanced further and the type A gastritis was still present, but there was no sign of carcinoid recurrence.

Autoimmune Diseases↗

PubMed1999

Interleukin 12 protects from a T helper type 1-mediated autoimmune disease, experimental autoimmune uveitis, through a mechanism involving interferon gamma, nitric oxide, and apoptosis.

Pathogenic effector T cells in experimental autoimmune uveitis (EAU) are T helper type 1-like, and interleukin (IL)-12 is required for their generation and function. Therefore, we expected that IL-12 administration would have disease-enhancing effects. Mice were immunized with a uveitogenic regimen of the retinal antigen interphotoreceptor retinoid-binding protein, treated with IL-12 (100 ng/d for 5 d), and EAU was assessed by histopathology. Unexpectedly, IL-12 treatment failed to enhance EAU in resistant strains and downregulated disease in susceptible strains. Only treatment during the first, but not during the second, week after immunization was consistently protective. High levels of interferon gamma (IFN-gamma) were present in the serum during IL-12 treatment, but subsequent antigen-specific IFN-gamma production in protected mice was diminished, as were IL-5 production, lymph node cell proliferation, and serum antibody levels. Treated mice had fewer cells and evidence of enhanced apoptosis in the draining lymph nodes. Unlike wild-type mice, IFN-gamma-deficient, inducible nitric oxide synthase (iNOS)-deficient, and Bcl-2(lck) transgenic mice were poorly protected by IL-12, whereas IL-10-deficient mice were protected. We conclude that administration of IL-12 aborts disease by curtailing development of uveitogenic effector T cells. The data are compatible with the interpretation that IL-12 induces systemic hyperinduction of IFN-gamma, causing activation of iNOS and production of NO, which mediates protection at least in part by triggering Bcl-2 regulated apoptotic deletion of the antigen-specific T cells as they are being primed.

Animals↗

PubMed2002

The number of markers of pancreatic autoimmunity is proportional to the risk for type 1 diabetes mellitus in Italian and English patients with organ-specific autoimmune diseases.

An 11-year prospective study was carried out in 226 patients with organ-specific autoimmune disease (OSAD) coming from northern Italy and southern England. Patients were investigated for diabetes-related autoantibodies (ICAs, GADAbs, and IA2Abs) in order to evaluate the best immunological combination in predicting type 1 DM. One hundred twenty-eight patients were ICA positive (77 Italian and 51 English), and 98 were ICA negative. ICAs were detected by immunofluorescence technique on human pancreas, whereas GADAbs and IA2Abs were found by immunoprecipitation assay. During follow-up, 33 of 128 (25.8%) ICA(+) (26% of Italian and 25.5% of English) and 2 of 98 (2%) ICA(-) patients developed type 1 DM (17 with acute-onset, and 18 with non-acute-onset disease). Among ICA(+) patients, three subgroups were considered: ICA(+) alone; ICA and GADAb(+); ICA, GADAb, and IA2Ab(+). Patients who were only ICA(+) had a predictive value for type 1 DM of 4.7%, with an annual incidence of 0.7%, and a cumulative risk of 6%. ICA and GADAb(+) patients had a predictive value of 17.5%, with an annual incidence of 2%, and a cumulative risk of 20%. ICA, GADAb, and IA2Ab(+) patients had a predictive value of 72, with an annual incidence of 13%, and a cumulative risk of 87%. Patients having three immunological markers revealed a prevalence increased in HLA-DR3 and/or -DR4, but reduced in HLA-DR2 haplotypes. The risk for type 1 DM increased proportionally with the number of diabetes-related antibodies, which were also related to the presence of genetic markers of disease susceptibility.

Adult↗

PubMed2003

Aging, autoimmunity and arthritis: T-cell senescence and contraction of T-cell repertoire diversity - catalysts of autoimmunity and chronic inflammation.

Rheumatoid arthritis (RA), like many other autoimmune syndromes, is a disease of adults, with the highest incidence rates reported in the elderly. The immune system undergoes profound changes with advancing age that are beginning to be understood and that need to be incorporated into the pathogenetic models of RA. The age-related decline in thymic function causes extensive remodeling of the T-cell system. Age-dependent changes in T-cell homeostasis are accelerated in patients with RA. The repertoire of naive and memory T cells is less diverse, possibly as a result of thymic insufficiency, and it is biased towards autoreactive cells. Presenescent T cells emerge that are resistant to apoptosis and that often expand to large clonal populations. These cells are under the regulatory control of nonconventional costimulatory molecules, display potent effector functions, and appear to be critical in the synovial and extra-articular manifestations of RA.

Aging↗

PubMed2005

High frequency of skewed X-chromosome inactivation in females with autoimmune thyroid disease: a possible explanation for the female predisposition to thyroid autoimmunity.

CONTEXT: Autoimmune thyroid diseases (AITD) comprise Graves' disease (GD) and Hashimoto's thyroiditis (HT). They are characterized by loss of immunological self-tolerance and female preponderance. Theoretically, X chromosome inactivation (XCI) and resultant tissue chimerism could offer an explanation for the female predisposition to AITD. AIM: Our aim was to examine whether skewed XCI is associated with AITD. DESIGNS: We first conducted a classical case-control study of twin individuals with and without AITD, and then a case-control study of twin pairs discordant for AITD. PARTICIPANTS: Participants included 32 female twins with AITD and a control group of 96 healthy female twin individuals. METHODS: XCI analysis was performed by enzymatic predigestion of DNA with a methylation-sensitive enzyme followed by PCR of the polymorphic CAG repeat of the androgen receptor gene. The XCI pattern was classified as skewed when 80% or more of the cells preferentially inactivated the same X chromosome. MAIN OUTCOME MEASURES: We assessed the prevalence of skewed XCI. RESULTS: The frequency of skewed XCI in female twins with AITD, GD, and HT was 34, 37, and 31%, respectively, which was higher than the prevalence in the corresponding control populations, 11% (P = 0.003), 14% (P = 0.045), and 8% (P = 0.057), respectively. Similar results were found in twin pairs discordant for AITD. Overall, skewed XCI was associated with an increased risk of developing AITD, with an odds ratio of 9.0 (95% confidence interval, 1.64-49.4) (P = 0.022). CONCLUSION: These observations suggest a possible role of XCI in the etiology of AITD and may in part explain the female preponderance of AITD.

Adult↗

PubMed1998

Linkage analysis of candidate genes in autoimmune thyroid disease: 1. Selected immunoregulatory genes. International Consortium for the Genetics of Autoimmune Thyroid Disease.

Graves' and Hashimoto's diseases are autoimmune thyroid diseases in which the genetic contribution is complex. For this reason, identification of necessary susceptibility genes has been difficult. However, a number of immunoregulatory genes have been implicated by association studies, including: CTLA-4, a recently described protein involved in antigen presentation, located on chromosome 2q33; the T-cell receptor V alpha and V beta gene complexes, located on 14q11 and 7q35, respectively; and the Ig gene complex (IgH), located on 15q11. We used polymorphic microsatellite markers located within these genes, or gene complexes, to test for linkage (rather than association), to each of these candidates. Using markers within the loci allowed us to assume a fixed recombination fraction of 0.01 in the tested model. Three hundred eight subjects from 48 multiplex families were studied, with 142 affected subjects. Using this set of families, we have previously shown evidence of linkage with a major susceptibility locus for Graves' disease (GD-1) on 14q24.3-31, with a maximum lod (logarithm + odds) score of 2.1, at a penetrance of 80% and with a dominant mode of inheritance. In the present study, we obtained consistently negative lod scores for each of the candidate genes, assuming either dominant or recessive modes of inheritance. These data, therefore, showed evidence against linkage with all the candidate genes. Unlike association studies, linkage analyses detect major genetic influences on disease susceptibility exerted by the linked loci. The lack of linkage for the immunoregulatory genes that were studied indicated, therefore, that they were not major contributors to disease etiology.

Abatacept↗

PubMed1998

Linkage analysis of candidate genes in autoimmune thyroid disease. II. Selected gender-related genes and the X-chromosome. International Consortium for the Genetics of Autoimmune Thyroid Disease.

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are autoimmune thyroid diseases (AITD) in which multiple genetic factors are suspected to play an important role. Until now, only a few minor risk factors for these diseases have been identified. Susceptibility seems to be stronger in women, pointing toward a possible role for genes related to sex steroid action or mechanisms related to genes on the X-chromosome. We have studied a total of 45 multiplex families, each containing at least 2 members affected with either GD (55 patients) or HT (72 patients), and used linkage analysis to target as candidate susceptibility loci genes involved in estrogen activity, such as the estrogen receptor alpha and beta and the aromatase genes. We then screened the entire X-chromosome using a set of polymorphic microsatellite markers spanning the whole chromosome. We found a region of the X-chromosome (Xq21.33-22) giving positive logarithm of odds (LOD) scores and then reanalyzed this area with dense markers in a multipoint analysis. Our results excluded linkage to the estrogen receptor alpha and aromatase genes when either the patients with GD only, those with HT only, or those with any AITD were considered as affected. Linkage to the estrogen receptor beta could not be totally ruled out, partly due to incomplete mapping information for the gene itself at this time. The X-chromosome data revealed consistently positive LOD scores (maximum of 1.88 for marker DXS8020 and GD patients) when either definition of affectedness was considered. Analysis of the family data using a multipoint analysis with eight closely linked markers generated LOD scores suggestive of linkage to GD in a chromosomal area (Xq21.33-22) extending for about 6 cM and encompassing four markers. The maximum LOD score (2.5) occurred at DXS8020. In conclusion, we ruled out a major role for estrogen receptor alpha and the aromatase genes in the genetic predisposition to AITD. Estrogen receptor beta remains a candidate locus. We found a locus on Xq21.33-22 linked to GD that may help to explain the female predisposition to GD. Confirmation of these data in HT may require study of an extended number of families because of possible heterogeneity.

Aromatase↗

PubMed1995

Differential immunogenetic determinants of polyclonal insulin autoimmune syndrome (Hirata's disease) and monoclonal insulin autoimmune syndrome.

The insulin autoimmune syndrome (IAS), or Hirata's disease, is characterized by the combination of fasting hypoglycemia, high concentration of total serum immunoreactive insulin, and presence of autoantibodies to native human insulin in serum. Autoantibody production is classified as monoclonal or polyclonal, with the majority of IAS cases classified as polyclonal. Previously, we observed a striking association between the human leukocyte antigen (HLA) class II alleles DRB1*0406/DQA1* 0301/DQB1*0302 and Japanese IAS patients with polyclonal insulin autoantibodies (IAAs) and T-cell recognition of human insulin in the context of DRB1*0406 molecules. Because of such a strong HLA association in IAS, we performed intra- and interethnic studies on IAS-associated DRB1 alleles and searched for the critical amino acid residue(s) for IAS pathogenesis. Glutamate at position 74 in the HLA-DR4 beta 1-chain was presumed to be essential to the production of polyclonal IAA in IAS, whereas alanine at the same position of the HLA-DR beta 1-chain might be important in the production of monoclonal IAA.

Adult↗

PubMed2001

Pancreatic biopsy as a procedure for detecting in situ autoimmune phenomena in type 1 diabetes: close correlation between serological markers and histological evidence of cellular autoimmunity.

To better understand the pathogenesis of type 1 diabetes, we have developed pancreatic biopsy under laparoscope for recent-onset type 1 diabetic patients. The patients included 29 acute-onset type 1 diabetic patients, 5 latent-onset type 1 diabetic patients, and 1 type 2 diabetic patient. Their median age was 28 years, and the duration of diabetes at the time of biopsy was approximately 3 months. In 31 of 35 patients, we could obtain the pancreas tissue by punching. No serious complications, such as heavy bleeding, peritonitis, or pancreatitis, have been experienced. Pneumoderma was observed in two patients, and abdominal dull pain had continued for 2 days in two patients. However, special treatment was not necessary for these complications. T-cell-predominant infiltration to islets (insulitis) and hyperexpression of major histocompatibility complex class I antigens on islet cells were the two major findings and were observed in 17 of 29 recent-onset type 1 diabetic patients. These findings could be regarded as evidence of immune attack against beta-cells, and their presence was closely correlated with the presence of either anti-GAD or anti-IA-2 antibodies (P = 0.02). In conclusion, pancreatic biopsy under laparoscope is a safe procedure without serious complications, according to our findings, for detecting in situ autoimmune phenomenon in recent-onset type 1 diabetic patients.

Adolescent↗

PubMed2005

On the edge of autoimmunity: T-cell stimulation by steady-state dendritic cells prevents autoimmune diabetes.

Targeting of antigens to immature dendritic cells has been shown to result in antigen-specific T-cell tolerance in vivo. In the INS-HA/TCR-HA transgenic mouse model for type 1 diabetes, we tested the potential of the dendritic cell-specific monoclonal antibody DEC-205 conjugated to the hemagglutinin (HA) antigen (DEC-HA) to prevent disease onset. Whereas untreated INS-HA/TCR-HA mice all develop insulitis, and approximately 40% of these mice become diabetic, repeated injection of newborn mice with DEC-HA protected almost all mice from disease development. Histological examination of the pancreata revealed significant reduction of peri-islet infiltrations in DEC-HA-treated mice, and the islet structure remained intact. Moreover, HA-specific CD4+ T-cells from anti-DEC-HA-treated INS-HA/TCR-HA mice exhibited increased expression of Foxp3, cytotoxic T-lymphocyte-associated antigen-4, and the immunosuppressive cytokines interleukin-10 and transforming growth factor-beta. The findings indicate that targeting of the HA antigen to immature dendritic cells in vivo leads to a relative increase of antigen-specific Foxp3+ regulatory T-cells that suppress the development of type 1 diabetes. Our results provide a basis for the development of novel strategies focusing on prevention rather than treatment of autoimmune diseases.

Animals↗

PubMed2006

Targeted disruption of CD38 accelerates autoimmune diabetes in NOD/Lt mice by enhancing autoimmunity in an ADP-ribosyltransferase 2-dependent fashion.

Ubiquitously expressed CD38 and T cell-expressed ADP-ribosyltransferase 2 (ART2) are ectoenzymes competing for NAD substrate. CD38 exerts pleiotropic actions in hemopoietic and nonhemopoietic compartments via effects on calcium mobilization. ART2 is an ADP-ribosyltransferase on naive CD4+ and CD8+ T cells. ART2-catalyzed ADP-ribosylation of the P2X7 purinoreceptor elicits apoptosis. Transfer of a genetically disrupted CD38 allele into the autoimmune diabetes-prone NOD/Lt background accelerated diabetes onset in both sexes, whereas transfer of a disrupted ART2 complex had no effect. However, the fact that the accelerated pathogenesis mediated by CD38 deficiency required ART2 activity was demonstrated by combining both ART2 and CD38 deficiencies. Reciprocal bone marrow reconstitution studies demonstrated accelerated diabetes only when CD38-deficient bone marrow was transferred into CD38-deficient recipients. Neither decreases in beta cell function nor viability were indicated. Rather, the balance between T-effectors and T-regulatory cells was disturbed in CD38-deficient but ART2-intact NOD mice. In these mice, significant reductions in total viable CD8+ T cells were observed. This was accompanied by an age-dependent increase in a diabetogenic CD8 clonotype. This in turn correlated with impaired T-regulatory development (10-fold reduction in Foxp3 mRNA expression). These changes were corrected when CD38 deficiency was combined with ART2 deficiency. Both ART2-deficient and CD38/ART2 combined deficient T cells were resistant to NAD-induced killing in vitro, whereas CD38-deficient but ART2-intact T cells showed increased sensitivity, particularly the CD4+ CD25+ subset. Unexpectedly, diabetes development in the combined CD38/ART2 stock was strongly suppressed, possibly through epistatic interactions between genes linked to the targeted CD38 on Chromosome 5 and the ART2 complex on Chromosome 7.

ADP Ribose Transferases↗

PubMed1999

Strain variation in autoimmunity: attempted tolerization of DA rats results in the induction of experimental autoimmune encephalomyelitis.

This paper reports that DA rats develop experimental autoimmune encephalomyelitis (EAE) when immunized with encephalitogenic myelin basic protein (MBP) peptide (MBP63-81) in IFA. In contrast, most rodent strains are tolerized by this procedure. Doses as low as 5 micrograms peptide + IFA induced EAE in DA rats. Lewis (LEW) rats did not develop EAE, even after immunization with 100 micrograms encephalitogenic peptide (MBP68-86) + IFA, but were rendered tolerant to EAE. DA rat T cells proliferated to peptide, and proliferation was inhibited by CTLA4Ig, and by anti-B7.1 and anti-B7. 2 mAbs. This indicates that the ease of induction of EAE in this strain does not reflect a decreased requirement for T cell costimulation through the B7/CD28 costimulatory pathway. The inhibitory effect of CTLA4Ig was abrogated in the presence of anti-TGF-beta-neutralizing Ab. An encephalitogenic DA T cell line expressed mRNA for the Th1 cytokines IFN-gamma and TNF-alpha, as well as IL-10, and secreted these cytokines. In contrast, a T cell line from peptide + IFA-immunized LEW rats (which did not develop EAE) failed to secrete these cytokines. Although this line did not express TNF-alpha or IL-10 mRNA, IFN-gamma mRNA was detected, suggesting posttranscriptional regulation of IFN-gamma expression. Attempts to induce unresponsiveness in DA rats with encephalitogenic peptide-coupled splenocytes were also unsuccessful.

Amino Acid Sequence↗

PubMed1976

Autoimmune murine thyroiditis. VIII. Role of different thyroid antigens in the induction of experimental autoimmune thyroiditis.

Mice of the C57Br strain, which are susceptible to the induction of autoimmune thyroiditis with mouse thyroglobulin, and C57Bl mice, which are resistant, were immunized with human and rabbit thyroglobulins in Freund's complete adjuvant. Susceptible strain C57Br developed higher degrees of thyroid infiltration than the resistant strain. The results indicate that the responses to xenogeneic (foreign) thyroglobulins parallel allogeneic and syngeneic (mouse) thyroglobulin. BSVS mice, which are highly susceptible to thyroiditis, were immunized with mouse thyroid extract from five different mouse strains including syngeneic antigen. Recipients of C57Bl and DBA thyroid extracts showed lower indices of pathology than recipients of similar extracts from C3H, BSVS and non-inbred CF-1 mice. The results suggest that there is a difference in the immunogenicity of mouse thyroid extracts from different strains. Purified thyroglobulin was prepared from congenic strains B10.D2 (H-2d, resistant) and B10Br (H-2k, susceptible). H-2k thyroglobulin gave a greater response in both H-2k and H-2d mice than H-2d thyroglobulin.

Animals↗