摘要:

The treatment of young NOD mice with continuous anti-CD4 mAb administration has previously been shown to prevent insulitis from developing. It has also been shown that insulitis, once present, can be abolished by anti-CD4 mAb treatment, but that the insulitis recurs after treatment stops. We have studied the effect of treating young NOD/Wehi mice with a limited course of anti-CD4mAb to determine if any long term prevention of insulitis ensued.Anti-CD4 mAb (H129.19) was given i.p. weekly to 10 female NOD/Wehi mice from 25–100 days of age. Control mice received no treatment. The pancreases of the mice were examined histologically at 100 and 180 days of age and severity of insulitis graded from 0–100%The insulitis grade in treated mice at 100 days was 5±2% compared with 29 + 26% in age matched control mice (p<0.01). At 180 days of age the insulitis grade in treated mice was 29±23% compared with 47±22% in age matched controls (NS).Thus insulitis was prevented from developing by early treatment with anti-CD4 mAb but developed later when treatment was stopped. Early anti-CD4mAb treatment does not therefore appear to produce a tolerant state so averting insulitis development and, insulitis can still develop in older NOD mice.

ISSN:0891-6934    

DOI:10.3109/08916938909034354

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

The ontogeny and the function of rheumatoid factors (RF) are poorly understood. Here we describe a stable neonatal hybridoma cell line of BALB/c origin that secretes a RF autoantibody of the IgM class. By a series ofin vitroassays we determined that this RF reacts specifically with the murine IgGl heavy chain. It also binds IgG of several mammalian species. By using mutant IgGl molecules, the reactive epitope was mapped to the CH3 domain of the constant region of IgGl. These findings indicate that clones with reactivity to autologous IgGl exist in normal mice at birth.

ISSN:0891-6934    

DOI:10.3109/08916938909034355

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

Lymphoid irradiation is known to prevent spontaneous autoimmune diabetes in susceptible BB rats. The present studies investigated further the effects of radiation in diabetes prone (DP) and resistant (DR) BB/Wor rats, and histocompatible Yoshida (YOS) rats. Single doses of total body gamma irradiation (125–600 rads) induced diabetes within 22–44 days in 20 of 102 (20%) 30 day old DR rats,<1% of which develop the disease. Radiation was also associated with (1) a reduction in the ratio of W3/25+to OX8+peripheral blood lymphocytes within 2 weeks, and (2) a decreased percentage of lymph node cells expressing the RT6.1 surface alloantigen 3–4 weeks after treatment. Similar doses of irradiation did not alter the frequency or age at onset of diabetes in DP rats, and did not induce diabetes in YOS rats. When a single dose of 250 or 500 rads of gamma irradiation was followed by injection of mitogen activated spleen cells from acutely diabetic rats to adoptively transfer diabetes, 16 of 19 (84%) DR and 8 of 14 (57%) YOS rats became diabetic. Long term exposure to ultraviolet irradiation (UVB) did not alter the frequency or age at onset of diabetes in either DP or DR rats. We conclude that there may exist a population of regulatory cells relatively sensitive to gamma irradiation that play a role in determining the susceptibility of rats to autoimmune diabetes mellitus.

ISSN:0891-6934    

DOI:10.3109/08916938909034356

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

In addition to a lupus-like syndrome and massive T cell proliferation, MRL-1pr/1pr (MRL/1) mice develop an arthritic process very similar serologically and histologically to human rheumatoid arthritis (RA). Recently, we have developed in DBA/1 mice an experimental model of autoimmune arthritis (EAA) which shares clinical features with RA, by injecting homologous type II collagen (CII). In order to investigate the possible relationship between the spontaneous polyarthritis of MRL/1 mice and collagen induced EAA, we immunized MRL/1 mice with mouse (M) CII. Our findings revealed that the injection of 100 /jg M-CII in young or old MRL/1 mice did not modify the articular pathology which spontaneously develops in non-injected mice. Circulating autoantibodies to native M-CII were found in the sera of immunized young mice but were not detected in non injected or immunized old mice. Conversely, denatured alpha 1 (II) chains or CB peptides derived from M-CII were recognized by most of the MRL/I sera whether mice had been immunized or not. The incidence of positive sera as well as the intensity of the response evaluated by Western blot analysis increased with the age of the mice. Taken together, our data suggest that, even if the injection of homologous CII in MRL/1 mice may accelerate the onset of joint pathology, the spontaneous disease arises independently of an autoimmune response against native CII

ISSN:0891-6934    

DOI:10.3109/08916938909034357

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

In order to detect whether micro-organisms could initiate the autoimmune process in Graves' disease we have studied the temporal and spatial distribution of 857 cases of hyperthyroidism occurring in a community over ten years. Cases were identified through biochemistry laboratory records and following the exclusion of patients with toxic nodular goitre or with insufficient clinical data there were 599 with Graves' disease - an average annual incidence of 15.9 per 100,000. There was a tendency for cases to present in the summer months. The reported onset of symptoms, however, peaked in December and June. There was no evidence of clustering of cases in space and time using two different statistical methods. Incidence rates doubled between 1976 and 1980 and then declined - a trend that could neither be explained by changes in laboratory or clinical diagnosis nor did it correlate with any pattern of microbial disease in the area.We conclude that it is unlikely that infections that behave in an epidemic manner have a causative role in triggering Graves' disease.

ISSN:0891-6934    

DOI:10.3109/08916938909034358

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

A sensitive and highly specific ELISA assay was developed to determine the anti-myosin humoral immune response (AMA) in various heart diseases: acute viral myocarditis, infective endocarditis, acute myocardial infarction, and valve and coronary bypass surgery. The mean study entry AMA titer of each patient group was already significantly increased compared with age matched controls. During further follow-up (90 d) all the groups except for endocarditis showed a significant increase of AMA titer compared with their entry titer. Anti-myosin antibody titer were higher after cardiac surgery than after myocardial infarction or inflammatory heart disease. These results suggest that anti-myosin immune response is not limited to infectious processes in which the pathogen induces antibodies which cross-react with heart constituents but is merely caused by direct cardiac injury. Myosin as a major compound of heart cellular proteins turned out to be a good candidate to trigger immune response after cardiac injury.

ISSN:0891-6934    

DOI:10.3109/08916938909034359

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

To examine the effect of the major histocompatibility locus (HLA) and the duration of insulin-dependent diabetes (IDDM) on immune responses to insulin we assayed insulin induced proliferation of blood mononuclear cells and measured insulin antibodies in 66 patients with newly diagnosed and in 56 patients with longstanding IDDM matched for the age at onset (≤15 yrs). In up to two thirds of the patients blood mononuclear cells responded to insulins by proliferation, and insulin antibodies were found in two thirds of patients with IDDM of long duration. Insulin proliferation or antibodies were not associated to any particular HLA antigen. The frequency of HLA-DR3 in patients with newly diagosed IDDM was not increased unlike in patients with IDDM of long duration. In addition, HLA-B8 was associated to HLA-DR3 nearly twice as often in patients with newly diagnosed IDDM as in patients with longstanding IDDM. Thus, patients with IDDM of recent onset and diagnosed within the last three years more frequently responsed to insulin by proliferation and less often had HLA-DR3 than patients with IDDM of long duration and diagnosed about 20–25 years earlier.

ISSN:0891-6934    

DOI:10.3109/08916938909034360

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

Considering the high frequency of autoimmune disorders in Turner's syndrome and the close relationship between autoimmunity, HLA and immunoglobulin constant region gene polymorphisms, we studied 46 patients with Turner's syndrome, by determination of autoantibodies, HLA histoglobulins and Gm and Km allotypes. OSA and in particular PCA resulted significantly more frequent in patients than in the controls. A higher frequency of HLA-A31, B38 antigens and of blanks at HLA-A locus was found in Turner's subjects than in the controls. A31 was significantly more frequent in autoantibody positive patients while B38 was more frequent in autoantibody negative Turner's subjects than in the controls. DR4 antigen was present only in autoantibody negative patients. Gm 3; 23; 5* phenotype was significantly less frequent, while Gm 3; 5* phenotype was more frequent in patients than in controls. Our data confirm the higher incidence of autoimmunity disorders in Turner's syndrome than in normal subjects. Particular HLA and immunoglobulin types seem to mark this condition. The increase in the blank frequency at A locus could be explained by the presence of a rare antigen at HLA-A locus or a particularly elevated homozygous condition in these subjects.

ISSN:0891-6934    

DOI:10.3109/08916938909034361

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

The BB rat is a widely used animal model for the study of insulin dependent diabetes. An enzyme linked immunosorbent assay, using purified rat insulin, was used to measure serial insulin autoantibodies (IAA) levels in coded sera from the BB/W/D rat colony in order to establish the time course of IAA. The animals included 26 diabetes-prone BB rats, six diabetes-resistant BB rats and six Wistar controls. There was an increase in both IAA frequency and titre with time in the diabetes-prone group: none were positive at 45 days, 17/19 (89%) were positive by day 90 and all were positive thereafter. Similar results were observed in the diabetes-resistant BB group (0/6 positive at day 51, 6/6 positive at day 90). None of the Wistar controls were positive at 105 days, although occasional positive sera were observed at 120 days. IAA seem to be acquired early on in the majority of BB rats, both diabetes-prone and diabetes-resistant, and much later, if at all, in controls. A clear homology of the MHC genes exists in both BB rat sublines, thus IAA appear to be a strain related phenomenon rather than a marker for IDDM.

ISSN:0891-6934    

DOI:10.3109/08916938909034362

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

Human monoclonal antibodies produced by Epstein Barr (EB) virus transformation and/or cell fusion are frequently IgM antibodies which tend to cross react with a range of antigens and often bear little relationship to the highly specific IgG antibodies associated with human autoimmune disease. By fusing EB virus transformed B lymphocytes from a Hashimoto patient with a mouse myeloma line and selecting for synthesis of IgG class thyroglobulin (Tg) antibody, we have developed a hybridoma (VB/5) secreting Tg antibody of IgG2 subclass and lambda light chain type which has the characteristics of a monoclonal antibody on isoelectric focussing. The antibody has a high affinity for human Tg and recognises Tg from other primates but not non-primate Tg. However, it does not react with human thyroid peroxidase or a panel of other autoantigens.In terms of affinity constant, functional affinity and affinity heterogeneity, the antibody closely resembles the IgG2 lambda Tg antibody present in the serum of the Hashimoto patient whose B lymphocytes were used to develop the hybridoma. In addition to providing a useful reference standard for Tg antibody IgG subclass assays, VB/5 antibody and the hybridoma line provide a valuable starting point for detailed studies of Tg autoantibodies and the genes coding for the variable regions of their heavy and light chains.

ISSN:0891-6934    

DOI:10.3109/08916938909034363

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor