摘要:

Susceptibility to rheumatoid arthritis is, in part, conferred by genetic factors. Previous studies have suggested that inheritance of a particular allele of a restriction fragment length polymorphism (RFLP) detected in the T cell receptorβ(TCRβ) gene complex is associated with rheumatoid arthritis (RA). We have specifically tested this hypothesis in ethnically and geographically matched populations of RA patients and controls. We were unable to confirm previous observations of a TCRβassociation with RA even after stratifying our study and control populations by HLA type.

ISSN:0891-6934    

DOI:10.3109/08916939209150312

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Renal lesions at the chronic phase of MHC class-II-disparate graft-versus-host reaction (GVHR) were examined. To induce GVHR, C57BL/6 (B6) spleen cells were injected twice into either (B6xbml2)F1 (class-II-disparate), (B6xbml)F1 (class-I-disparate) or (bmlxbml2)Fl mice (class-I+II-disparate). for comparison, (C57BL/10xDBA/2)F1 (BDF1) mice injected with DBA/2 spleen cells were also used.(B6xbml2)F1 and BDF1 recipients showed marked elevation of anti-DNA antibodies, circulating immune complexes (CIC) and the number of immunoglobulin producing cells (IgPC). At 20 weeks after cell injection, severe immune complex glomerulonephritis (ICGN) was observed in (B6xbml2)F1 recipients, but was far less severe in (bmlxbml2)F1 recipients and was not observed in (B6xbml)F1 recipients. ICGN was also observed in BDF1 recipients at 12 weeks after cell injection. By immunofluorescent microscopy, IC deposition was detected along the capillary loops and also in the mesangial area in (B6xbml2)F1 recipients, while BDF1 recipients showed only a capillary pattern. By light microscopy, the renal lesion of (B6xbml2)Fl recipients appeared similar to those of BDF1 recipients. Histologically, (B6xbml2)F1 recipients serve as a good model for lupus glomerulonephritis induced by class-II-disparate GVHR.

ISSN:0891-6934    

DOI:10.3109/08916939209150313

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Thyroiditis occurs in about 50% of diabetic Bio Breeding/Worcester (BBAV) rats. In order to investigate the earliest stages of lymphocyte homing to the thyroid gland in the development of experimental autoimmune thyroiditis, we measured the amount of trapping of peripheral blood lymphocytes (PBL) from BBAV rats to the thyroid gland of syngeneic recipient animals. PBL, from donor normal or diabetic BBAV rats, labelled with 5lCr, were injected, i.v., into normal,“potentially diabetic”or diabetic BBAV recipients. After 24 hr the rats were sacrificed and the radioactivity of selected individual organs counted. Results were calculated as % binding of 5lCr-labelled PBL/unit weight of tissue and expressed as a binding index by comparing to binding to recipient blood lymphocytes. A significant binding index was taken as>1.0. PBL from diabetic or normal donor BBAV rats were shown to bind significantly to the thyroid gland of 8 out of 19“potentially diabetic”or diabetic recipient syngeneic rats, but to none of the normal (non diabetic) recipients tested. Sixty percent of“potentially diabetic”BBAV rats and 50% of diabetic rats at 3-4 months of age showed a significant level of binding of donor lymphocytes from syngeneic diabetic or normal animals to their thyroid gland, while, at 5-6 months the proportion of recipient rats giving positive tests was much less (17%). The source of the donor lymphocytes (diabetic, or normal) did not significantly influence the binding. Lymphocyte binding to pancreas was not significantly greater than to control tissues. These data suggest that target specific binding of lymphocytes to the thyroid gland my be detected early (at 3-4 months) in those BBAV rats which will subsequently develop diabetes and that the abnormality resides in the thyroid gland rather than the circulating lymphocytes. The findings support the idea that there may be a“homing”receptor on the thyroid cell, accounting for the initial lymphocyte infiltration in this organ, of diabetic BBAV rats which later develop thyroiditis.

ISSN:0891-6934    

DOI:10.3109/08916939209150314

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Cytofluorometric analysis using specific monoclonal antibodies directed against the T cell antigens Thy-1.2, CD4, CD8, CD4V/J(8.1+8.2+8.3), and the antigen Mac-1 expressed by mature macrophages and NK cells were used to characterize and quantify the phenotypes of (1) unfractionated and Percoll gradient fractionatedin situislet immune cells isolated from prediabetic and diabetic female NOD mouse spleens. We found in prediabetic female mice that the majority (-70%) of thein situislet immune cells were Thy-1.2 positive T cells. CD4 positive T cells (-40%) were the most abundant phenotype together with double negative T cells (-20%). The percentages of CD8 positive T cells were -10%, and only -4% of the immune cells were Mac-1 positive. The percentages of CD4V/3(8.1+8.2+8.3) positive and double negative T cells in diabetic spleens were significantly higher in comparison to prediabetic spleens. In C57B1/6J control nondiabetic mice the percentage of double negative T cells in the spleens was significantly 4-fold lower when compared to diabetic NOD spleens. The specific cytolytic activity mediated byin situislet immune cells against 51Cr-labeled dispersed syngeneic single-cell islet cells at an effector to target ratio of 20 was twenty- to thirty-fold higher than that mediated by prediabetic splenic lymphoid cells. It is concluded that prediabetic NOD mousein situislet immune cells are mostly CD4 positive and double negative T cells, and that CD4 and CD8 positive T cells in the intra-islet infiltrate warrants further evaluation as potential effector T cells in target J-cell destruction.

ISSN:0891-6934    

DOI:10.3109/08916939209150315

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Inheritance of Graves' disease has been linked to the HLA-DR3 gene product which may function in some specific way in antigen presentation. To determine whether the first extracellular domain of this protein, which is specifically involved in antigen presentation, has the same sequence in patients with Graves' disease and in normal individuals, we have amplified the second exon using the polymerase chain reaction, and then cloned and sequenced the DNA segment. In eight subjects with Graves' disease, sequences identical to prototypic reported sequence for DRB 1*0301 were recovered, and in two individuals sequences varied by a few nucleotides, leading to 1-3 amino acid substitutions which did not occur in a pattern. Sequences identical to the prototypic sequence known as DRB3*0101, also previously known as DRw52, were also recovered. Thus the HLA-DRB1 and B3 genes present in patients with autoimmune disease appear to be the same as those present in the general population. These observations indicate that a unique allele is not present in patients with autoimmune disease, but rather that the normal DR3 allele itself, in a manner yet to be described, increases the probability of developing autoimmune thyroid disease.

ISSN:0891-6934    

DOI:10.3109/08916939209150316

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Homozygosity for either the lymphoproliferation (lpr) or the generalized lymphoproliferative disease (gld) mutation of mice causes the development of strikingly similar autoimmune and lymphoproliferative syndromes. The relationship between thelprandgldmutations was studied by grafting B6gldspleen cells (SC) to athymic B6nude lprmice (B6nulpr)or to B6nude(B6nu)mice as controls. The injection of B6gldSC, but not of B6wildSC, to B6nulprmice caused a prolongation of survival of the short living B6nulprrecipients. This was associated with elevated anti-single stranded DNA antibody titers and a serum hyperglobulin-emia, as well as by a splenomegaly which was nearly as high as in genetically B6gldmice, and by a marked lymphadenopathy (though milder than that of B6gldmice). In contrast the[gldnu]chimaeras showed a more attenuated form ofgld-inducedsyndrome. These results suggest that thelprenvironment supplied in athymiclprrecipients is compatible with-and may even favour-the development of the gld-induced syndrome.

ISSN:0891-6934    

DOI:10.3109/08916939209150317

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

A monoclonal natural thymocytotoxic autoantibody NTA204 established from an autoimmune-prone NZB mouse reacted with the majority of thymocytes, all peripheral B cells, granulocytes and bone marrow myeloid cells, but not with peripheral resting T cells of normal mice. In aged NZB/W F1 mice with overt autoimmune disease, the population of NTA2044 CD4* CD25 T cells was remarkably increased. The NTA204 antigen could be induced on splenic T cells from normal healthy mice as early as 3 hr after the initiation of culture with stimulant Con A, and was expressed on the vast majority in the 48-hr culture. The expression preceded that of other T cell activation antigens tested, CD25 and CD45R. Cell cycle analysis suggested that NTA204 is expressed at an early phase of Gl A. T cells, particularly CD8+ T cells, in the allogeneic mixed lymphocyte culture (MLC) could be divided into two populations, NTA204* and NTA204. By immunohistochemical analysis, 30% of NTA204* CD8+, but few NT204 CD8+ T cells were intensely positive for large cytoplasmic granules of perforin, an important cytolytic mediator of cytotoxic T cells. Thus the increased population of NTA204* T cells in aged NZB/W F1 mice appear to be activated T cells and might be at least partly involved in the pathogenesis of disease in these mice. Immunoblotting analysis of Con A-activated splenic T cells showed that NTA204 molecules have a molecular mass of 49 Kd.

ISSN:0891-6934    

DOI:10.3109/08916939209150318

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

A brief exposure of pancreatic islets to the cytokine interleukin-1β(IL-lβ) induces an initial stimulatory phase, which is followed by inhibition of islet function and eventuallyβ-cell damage. In the present study we have investigated the effects of IRAP, a blocker of type I IL-1 receptor and actinomycin D, an inhibitor of DNA transcription, on both the stimulatory and inhibitory effects of IL-βon rat pancreatic isletsin vitro. The two test agents counteracted the initial stimulatory actions of IL-1βon both islet glucose-induced insulin release and glucose oxidation rates. Furthermore, cycloheximide, an inhibitor of protein synthesis, could also prevent the early IL-l/?-induced stimulation of insulin release. When islets were exposed for 1 hr to IL-1βand studied after 12 hr, there was a 75% inhibition of glucose induced insulin release, a 50% decrease in glucose oxidation rates and a 30% decrease in (pro)insulin biosynthesis. These effects were completely counteracted by coincubation with IRAP or actinomycin D, but were not affected by coincubation with pertussis toxin. Islet exposure to IL-Ia also induced a 60-80% inhibition of glucose-induced insulin release after 12 hr. As observed with rIL-1β, IRAP was also able to block the suppressive effects of IL-1 a on islet function. Mouse islets exposed for 2 hr to IL-1βand studied after 12 hr presented a 50% decrease in the glucose-induced insulin release. This effect was completely blocked by coincubation with a rat monoclonal antibody generated against the type I mouse IL-1 receptor.These data suggest that most or all effects of IL-lβon rat pancreatic islets are dependent on binding to surface IL-1 receptors and activation of gene transcription. It remains to be clarified which are the second messengers generated following IL-1βbinding to its receptor and which are the gene(s) transcribed following pancreatic islet exposure to the cytokine.

ISSN:0891-6934    

DOI:10.3109/08916939209150319

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The murine strain MRL/1 spontaneously develops a systemic lupus erythematosus (SLE)-like syndrome. An increased number of T cells and polyclonal T helper cell activity has been described in these mice suggesting a potential role for 1,25-dihydroxyvitamin-D3[1,25-D3], an antiproliferative hormone selecting the T-helper lymphocyte subset. One month old MRL/1 mice were submitted or not to 1,25-D30.1μg for 4 weeks, then 0.15μg given i.p. every other day for 18 weeks while maintained on a low calcium chow. Dermatologic lesions, i.e. alopecia, necrosis of the ear and scab formation, were completely inhibited by 1,25-D3therapy. By 20 weeks, all mice had developed proteinuria. However, the degree of proteinuria was somewhat reduced in treated mice as assessed by urine protein/creatinine ratios (4 in treated vs untreated mice respectively). Moreover, a trend for a reduction in serum titers for anti-ssDNA antibodies was observed at 18 weeks. The active vitamin D metabolite had no effect on the development of the generalized lymphoid hyperplasia. Hypercalcemia developed when 1,25-D3was increased to 0.15/μg (2.62±0.12 vs 1.97±0.07 mmol/1, treated vs untreated mice respectively). These results suggest a beneficial role of 1,25-D3in the prevention or attenutation of some manifestations of murine SLE, a model sharing many immunologic features with human SLE.

ISSN:0891-6934    

DOI:10.3109/08916939209150321

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

A 54 y.o. woman presented with acute Coombs-negative hemolytic anemia at an outside hospital where she received 25 RBC transfusions and did not respond to prednisone or splenectomy. On transfer to our hospital, routine DAT and IAT were weakly positive, occasionally negative. When a modified“cold”antiglobulin test was employed, the result was strongly positive for IgG, weakly positive for C3d. Cold agglutinin titer was 32, and the Donath-Landsteiner test was negative. The autoantibody exhibited Praspecificity.The patient failed IV-IgG, high dose IV pulse steroids and cyclophosphamide, and continued to require daily transfusions. She responded 21 days after receiving daily plasma exchange (x3), with pulse cyclophosphamide on the third day, followed by escalating daily oral cyclophosphamide.

ISSN:0891-6934    

DOI:10.3109/08916939209150322

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor