摘要:

Autoimmunity to La(SS-B) and Ro(SS-A) is a paradigm for understanding the normal mechanisms of B cell and T cell tolerance and development of autoimmunity to clinically important sequestered autoantigens. Epitope mapping experiments have indicated that the autoantibody response is largely self antigen-driven but have failed to elucidate why these particular autoantigens are selected. Abnormal trafficking of La or Ro peptides in polarised epithelial cells and their presentation to autoreactive T cells, or selective release of ribonucleoproteins by injured epithelial cells, could explain the targeting of salivary and lacrimal epithelium in Sjogren's syndrome. There appears to be little, if any, immune tolerance to La in the T helper and B cell compartments. Both intra-and inter-molecular spreading of the autoimmune response have been observed for La. We present a model of recruited autoimmunity whereby capture and internalisation of La/Ro ribonucleoproteins by B cells and subsequent presentation of La or Ro determinants to autoreactive T cells could lead to inter-molecular spreading of the response.

ISSN:0891-6934    

DOI:10.3109/08916939409007981

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

In-vitro mouse thyroglobulin (MTg) activated spleen cells from immunized donor mice can induce experimental autoimmune thyroiditis (EAT) after transfer to recipient mice. The intrathyroidal cellular infiltrate consists primarily of mononuclear cells (lymphocytic EAT). Cells cultured with MTg together with anti-IL2R antibody induce EAT with a granulomatous hisopathology in which the thyroid infiltrate contains mononuclear cells (MNC) in addition to PMN's, histiocytes, and multinucleated giant cells. Flow cytometric analysis of intrathyroidal MNC infiltrates demonstrated that both CD4 + and CD8 + T cells infiltrate the thyroid in both lymphocytic and granulomatous EAT and that CD8 + T cells outnumber CD4 + T cells. There were usually increased numbers of PMN's in the granulomatous thyroids, but low number of Ig + and F4/80 + cells (macrophages) in the intrathyroidal infiltrate of both disease types. IL2R and Pgp-1 were expressed on both CD4+ and CD8+ intrathyroidal T cells. The majority of CD8 + cells were 1CAM +, LFA-1 +, and CD45RB + whereas only a small percentage of CD4 + intrathyroidal T cells expressed these markers. There were no major differences in intrathyroidal MNC phenotype between lymphocytic and granulomatous EAT. Depletion of CD8 + T cells in recipient mice did not reduce EAT severity and resulted in an increased percentage of intrathyroidal CD4 + T cells expressing 1L2R. These results suggest that CD8 + T cells are not functioning as effector cells in lymphocytic or granulomatous EAT.

ISSN:0891-6934    

DOI:10.3109/08916939409007982

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

We recently expressed the extracellular domain of the human TSHR (ETSHR) protein using a baculovirus expression system and purified it to homogeneity. The ETSHR specifically binds both TSH and antibodies to TSHR. In the present study, C57BL/6J, SJL/J, BALB/cJ and BlOBR.SgSnJ mice were immunized with the recombinant ETSHR or an equivalent amount of control antigen. All strains of mice produced high titers of antibody against the TSHR protein which were capable of blocking the binding of TSH to native TSHR. However, only BALB/cJ mice showed significantly elevated levels of thyroxine in their sera compared to the control mice. Similarly, BALB/cJ mice primed with ETSHR and then challenged with thyroid membranes showed significantly elevated levels of thyroxine. In addition, histopathological examination of thyroid glands from affected mice showed morphological changes characterized by hydropic and subnuclear vacuolar changes and focal scalloping, with no apparent inflammation or glandular destruction. Moreover, mice with elevated thyroxine levels showed increased in vivo thyroidal uptake ofl31Iodine. Together, these data suggest that BALB/cJ mice are susceptible to the induction of hyperthyroxinemia.

ISSN:0891-6934    

DOI:10.3109/08916939409007983

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

In mysathenia gravis (MG) autoantibodies directed against acetylcholine receptors (AChR), at the neuromuscular junction lead to muscle weakness. These antibodies are directed against extracellular determinants, predominantly on the AChR a subunits. Similar antibodies can be induced in animals by immunisation with purified AChR, but immunisation of mice with recombinant human a subunit or its extracellular domain has produced conflicting results. To study further the immunogenicity of the human a subunit we immunised four inbred stains (C57B1/6, SJL, BALB/c, SWR) with almost full-length recombinant a subunit, r37-429, and looked at B cell epitopes by mapping with smaller recombinant fragments and synthetic peptides. The majority of anti-r37-429 antibodies bound to sequences within a region thought to be cytoplasmic,α325-368, and reacted with human AChR. In two C57B1/6 sera, only, most antibodies were directed against an extracellular region,α138-167, but the r3 7-429 used for immunisation of these two mice appeared to have lost the integrity of its cytoplasmic domain during preparation. Our results suggest that the antigenicity of the cytoplasmic region of the recombinant a subunit dominates the immune response in each of the four strains, and may even suppress the formation of antibodies to the extracellular domain. Moreover, although C57B1/6 and SJL mice were able to produce antibodies to al38-167, these antobodies did not react with intact AChR, and none of the mice became weak.

ISSN:0891-6934    

DOI:10.3109/08916939409007984

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

It is well known that healthy subjects carrying the HLA-B8, DR3 haplotype may show an impairment of immune system, the T cells being the most affected. To gain insight into the mechanism(s) of the impairment displayed by these subjects, efforts have been centered on the study of in vitro cytokine production because of the pivotal role played by these mediators in the activation and control of several immune functions. The available results indicate that the ability to produce interleukin-1 (IL-1), IL-2 and the soluble form of its receptor (sIL-2R) is impaired in HLA-B8, DR3 positive healthy subjects. To better characterize the cytokine production capacity of HLA-B8, DR3 positive subjects, we have investigated the pattern of in vitro production of IL-2, sIL-2R, IL-4, IL-6 andγ-interferon (γ-IFN) by mononuclear cells from HLA-B8, DR3 positive subjects after phytohaemoagglutinin stimulation. A significant decrease of IL-2, sIL-2R andγ-IFN production by HLA-B8, DR3 positive subjects was observed. No significant difference was instead found between the HLA-B8, DR3 positive subjects and the negative ones as regards IL-4 and IL-6 production. We suggest that this imbalanced cytokine production may well account for the pattern of immune response that may be observed in HLA-B8, DR3 positive subjects, i.e. a normal or increased humoral response in face of a low T cell immue responsiveness.

ISSN:0891-6934    

DOI:10.3109/08916939409007985

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

We have postulated that in vivo autologous mixed lymphocyte reactions (AMLRs) are one mechanism in the development of the intrathyroidal lymphocytic infiltration of human autoimmune thyroid disease. Such a mechanism would explain the significant numbers of self-reactive T cells present in thyroid infiltrates as evidenced by cloning studies. However, infiltrating T cells in a variety of autoimmune diseases including autoimmune thyroid disease, demonstrate bias in their use of T cell receptor (TcR) V gene families. In order to examine whether such TcR V gene bias may occur secondary to non-antigen specific in vivo AMLRs rather than secondary to specific autoantigen driven mechanisms we have examined the human TcR repertoire after prolonged AMLRs in vitro. Using 5 healthy donors in 1, 2 and 3 week AMLRs we showed stimulation indices of 3.1–6.5 after 3 weeks. The hTcR Vαand Vβgene repertoire was assessed using the PCR technique and revealed an almost complete repertoire of V gene families at the beginning of the studies while at the end of 3 weeks a mean of only 5.2 Vαgenes were transcribed. Less restriction was seen in the hTcR Vβrepertoire with a mean of 9 Vβgenes used. These data demonstrate that the AMLR is able to mimic the marked bias in hTcR V gene family use seen within the inflamamatory infiltrates of autoimmune diseases.

ISSN:0891-6934    

DOI:10.3109/08916939409007986

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

In chronic autoimmune thrombocytopenic purpura (AITP), an indirect monoclonal antibody immobilised platelet antigen (MAIPA) assay detected serum glycoprotein (GP) Ilb/IIIa antibodies in 16/39 (41%) cases. In patients with clinically active AITP, a direct MAIPA assay detected platelet-associated GP Ilb/IIIa kantibodies in 8/13 (62%) cases. Platelet bound and serum antibody concentrations suggested a high antibody affinity for platelet membrane glycoprotein Ilb/IIIa. Five AITP patients with platelet associated glycoprotein Ilb/IIIa antibodies were treated with intravenous anti D immunoglobulin. All showed an increase in platelet counts and a decrease in platelet associated autoantibody. These responses could be due to immunosuppressive anti-idiotype antibodies in anti D immunoglobulin.

ISSN:0891-6934    

DOI:10.3109/08916939409007987

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

The presencc of autoantibodies in the scra of patients with myocarditis has suggeted that autoimmunity is a sequela of myocarditis. In this study, we examined anti-vimentin antibodies in a murinc model of myocarditis. Four-week-old male DBA/2 mice were inoculated intraperitoneally with 10 plaque-forming units of encephalomyocarditis (EMC) virus. The surviving mice were killed on Days 0 (n = 7), 2 (n = 6), 5 (n = 6), 7 (n = 6), 9 (n = 6), 14 (n = 5), 60 (n -6) and 540 (n = 3) after virus inoculation. The presence of anti-vimentin autoantibodies in the sera of mice was determined by ELISA. The optical density (OD) of anti-vimentin IgG and IgM autoantibodies of day 0 mice was 0.03 i 0.03 and 0.12 i 0.08, respectively. when positive antibody was defined as over the mean value plus 2-standard deviations of the scra of day 0 mice, anti-vimentin IgG antibodies werc negative before day 5 but positive in all mice on day 9. Both IgG and IgM OD of the sera from day 9 mice (IgC; 0.26i0.12, IgM; 0.30k0.08) were significantly higher than thosc of the sera from day 0 mice (p<0.005) and decreased thereafter on day 14. In the chronic stage, five of six mice werc positive on day 60 and two of threc mice were positive on day 540. Although further studies arc needed to elucidate the pdthogcnetic role of anti-vimentin antibodies, these antibodies may be a parameter of the interstitial injury.

ISSN:0891-6934    

DOI:10.3109/08916939409007988

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

In Graves’disease an increased immunological activity against glycoconjugate antigens is observed. Since gangliosides seem to be important for thyroid stimulation we searched for the presence of antiganglioside antibodies in Graves’patients sera by the immunoenzymatic method. Antibodies against some of 12 different gangliosides used in this study were found in 22% of the patients. However, in most cases the titer of antiganglioside antibodies was very low. Only the serum from one patient reacted with FucGMl ganglioside at the dilution up to 1 : 1300. Anti-FucGM 1 antibodies were present in serum samples of this patient taken before and during the treatment when she was hyper-hypo- and euthyroid. The lack of relation of the anti-FucGM 1 antibody titer to the thyroid status of this patient, and the very low titer of antiganglioside antibodies in sera of some other patients, suggest that the presence of these antibodies has no close connection to the thyroid disease.

ISSN:0891-6934    

DOI:10.3109/08916939409007989

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939409007990

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor