ISSN:0891-6934    

DOI:10.3109/08916939008995725

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Supernatants of 5 day cultures of peripheral blood mononuclear cells (PBMC) stimulated by thyroid microsomal antigens (TMA), and liver microsomal antigens (LMA) have been utilized to induce HLA-DR expression on human thyroid epithelial cells (TEC). The PBMC were obtained from 8 normal control persons and 13 patients with autoimmune thyroid disease (AITD) (7 Graves' disease and 6 Hashimoto's thyroiditis). The TEC HLA-DR expression was measured by an enzyme-linked immunosorbent assay (EL1SA) technique. TEC HLA-DR expression was calculated as follows: (experimental optical density -control optical density) x 103; TEC HLA-DR index: % HLA-DR expression of IFNγ100 U/ml stimulation; and stimulation index (SI): TEC HLA-DR expression index induced by PBMC supernatants with antigen stimulation/TEC HLA-DR expression index induced by PBMC supernatants without antigen stimulation±100. Supernatants without antigen stimulation from both normal control subjects and patients were able to induce TEC HLA-DR expression only minimally: 36.7±32.6 (mean±SD) TEC HLA-DR index for normal controls and 21.3±15.5 TEC HLA-DR index for AITD (not significant). The SI curves of both TMA and LMA were significantly different between control and AITD using two-way ANOVA test (Plt;0.01). TMA-stimulated PBMC supernatants from the patients increased TEC HLA-DR expression when compared to basal level using paired t-test; TMA I ng/ml, SI 179±99,p<0.05. On the other hand, TMA-stimulated PBMC supernatants from normal controls decreased TEC HLA-DR expression; TMA 1 ng/ml, SI 78 + 23,p<0.05; TMA 10 ng/ml, SI 69±23,P<0.01; TMA 100 ng/ml, SI 69±35,p<0.05. In contrast, LMA-stimulated PBMC supernatants from patients neither increased nor decreased TEC HLA-DR expression compared to basal level. While IFNfM-indueed TEC HLA-DR expressiona was completely suppressed by anti-human IFNy antibody (98±2%), PBMC supernatant-induced TEC HLA-DR expression was less completely suppressed when anti-human IFNγantibody was added to the cultures (77±4%) (P<0.01 V.S. IFNγ). These results indicate that TMA stimulated PBMC from patients with AITD to secrete lympokine(s), presumably mostly IFNγ, which then lead to TEC HLA-DR expression. This phenomenon may reflect organ specific autosensitization of PBMC. Thus sensitized T lymphocytes from patients with AITD have the capacity to secrete such cytokines after stimulation with specific thyroid antigen, thus resulting in TEC HLA-DR expression. On the other hand, PBMC from normal controls did not have this capacity, which was reflected by the absence of sensitization to TMA and LMA.

ISSN:0891-6934    

DOI:10.3109/08916939008995726

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Based on recent structural analyses of monoclonal autoantibodies, it appears that a number of these antibodies express germ-line immunoglobulin variable region (V) genes with little or no somatic mutation. In addition, our group and others have noted the identity or near identity of some autoantibody-associated V genes to V genes apparently expressed preferentially in the fetal pre-B cell repertoire. To extend these data, we now report that the heavy and light chain V genes of an anti-cardiolipin antibody derived from a healthy individual display 99% nucleotide sequence homology with V genes expressed in early B cell ontogeny. Sequence comparisons indicate the likely use of fetal-restricted V genes by this autoantibody. Taken together with other data on autoantibody V gene usage, these findings provide further evidence for overlap between the autoantibody-associated and early ontogeny expressed V gene repertoires and suggest that natural autoreactivity may be instrumental in the development and maintenance of the normal immune repertoire.

ISSN:0891-6934    

DOI:10.3109/08916939008995727

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Autoantibodies directed at the platelet membrane glycoprotein lb (GPIb) can mediate a severe form of idiopathic thrombocytopenic purpura (ITP). The platelet-specific antibody from plasma of one patient (DM) with this form of ITP displays a public idiotype termed DMId. The DMId idiotype has been found in the plasma of several patients with ITP, usually in association with GPIb-specific autoantibodies. As a step in the understanding of the molecular genetics of this form of ITP we have determined the nucleotide sequences of expressed V region genes selected from a panel of five human lymphoblastoid cell lines derived from patient DM. Two of the lines secreted antibodies that bound GPIb, and three of the lines secreted antibodies that expressed DMId. The H chain sequences of the DMId-positive antibodies and of one of the GPIb-binding antibodies belong to the VH4 family. The second GPIb-binding antibody belongs to the VH1 family. All have multiple substitutions from previously published sequences giving these antibodies the appearance of having been antigen driven. These results are consistent with the hypothesis that autoantibodies in ITP arise from a“normal”immune response inappropriately directed at platelet antigens. Further, our results suggest that VH4 gene segments may be recruited preferentially into the DMId-positive, GPIb-specific autoantibody response.

ISSN:0891-6934    

DOI:10.3109/08916939008995728

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

T cells from rheumatoid synovium have been expandedin vitroas lines and clones using autologous Epstein-Barr virus-transformed stimulator cells. Both lines and clones recognized autologous class II MHC antigens in the absence of defined exogenous antigens i.e. the equivalent of the autologous mixed lymphocyte response. Surprisingly, despite their MHC specificity, several clones expressed CDS rather than CD4, but were not cytotoxic. The function of CD8 + T cells within synovium has not previously been defined; in view of their unusual phenotype, they may exert an immuno-modulating role upon the inflammatory response within the joint, by responding to the high density of class II MHC antigens expressed in the rheumatoid synovium.

ISSN:0891-6934    

DOI:10.3109/08916939008995729

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Human autoimmune thyroid cells“spontaneously”express MHC-class II antigens. These antigens have been assumed to trigger thyroid-specific helper T cell clones, leading in turn to the expansion of thyroid autoantibody-secreting B cells. Thyroid cells derived from non-autoimmune subjects do not express MHC-class antigens, but these can be readily induced with -γ-interferon. We have addressed the issue of whether it is sufficient for normal thyroid cells to bear class II antigens in order to trigger autologous T cells. We found that non-autoimmune thyrocytes expressing DR antigens fail to stimulate autologous resting T cells. However, proliferative activity and interleukin-2 secretion were observed when fresh T cells were first triggered by autologous non-T cells and then incubated with thyrocytes. More CDgthan CD4, cells proliferated in the T:thyrocyte cultures, but CD4cells were necessary for the proliferation and interleukin-2 secretion. Addition of antibodies to thyroglobulin or to DR antigens inhibited T cell proliferation and interleukin-2 secretion, thus pointing to T cell recognition of both thyroid-specific and DR antigens. Evaluation of the function of the thyroid stimulated T cells revealed very potent suppressor but negligible helper and cytotoxic activities. It would seem, therefore, that DR-restricted T cell activation by autologous antigen on non-autoimmune thyroid cells does occur, but since it results in enhanced suppression, its nature seems protective, thus leading to maintenance of immunological self-tolerance.

ISSN:0891-6934    

DOI:10.3109/08916939008995730

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The selective loss of insulin-producing pancreatic beta cells which occurs in IDDM has been postulated to result from lysis by beta cell-specific cytotoxic T lymphocytes (CTL). CTL typically recognise antigen in the context of MHC class I molecules, which are normally present at low levels on beta cells. However, hyperexpression of class I antigens on islet cells has been observed in the early stages of beta cell destruction in IDDM. Since interferon-γ”(IFN-γ) is known to increase class I expression on a number of cell types, we have investigated the responses of murine beta cells to this cytokine under various conditions. Two color immunostaining followed by FACS analysis showed that on average, only 14.9±3.1% of cultured beta cells were class I positive. However, a majority of beta cells could be induced to express class I after 24 hours of IFN-γtreatment, and maximal induction (80-90% positive) occurred after 48 hours. Importantly, increased class I expression on beta cells could be achieved with very low concentrations of IFN-γ(1-10U/ml). Expression of class II MHC was never detected under any of the conditions employed to up-regulate class I. Interestingly, although islet cells were only moderately susceptible to lysis by allospecific CTL, this susceptibility was markedly enhanced by prior exposure of the islets to IFN-γ. Taken together, these results suggest that beta cells are extremely susceptible to up-regulation of class I MHC molecules by IFN-γ, and that this property may render these cells particularly susceptible to lysis by autologous class I-restricted CTL. Since enhanced expression of class I frequently accompanies inflammatory responses and viral infections, this property of beta cells may account in part for their selective destruction in IDDM.

ISSN:0891-6934    

DOI:10.3109/08916939008995731

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

To evaluate changes in TSH receptor antibody after surgery in Graves' disease and its relationship with the degree of lymphocytic infiltration, serial serum levels of TSH receptor antibody were measured before and after the subtotal thyroidectomy in 50 patients with Graves' disease. In 22 (44%) out of 50 patients. thyrotropin binding inhibitor immunoglobulin (TBII) levels gradually decreased and disappeared completely within 12 months after surgery (TBII disappearing group). Twenty-eight (56%) patients showed persistent TBII activity and their levels were not changed until 12 months after surgery (TBII persistent group). The changes of thyroid stimulating antibody (TSab) levels were very similar to those of TBII in both groups. The thyroidal lymphocytic infiltration was more prominent in the TBII disappearing group. The degree of the decrease of TBII levels after surgery correlated with the grade of thyroidal lymphocytic infiltration. There was no significant difference of TSH receptor antibody (both TBII and TSab) levels between the thyroid and peripheral venous blood. These data suggest that the persistence or disappearance of TSH receptor antibody after surgery may reflect the difference between patients in whom the thyroid is the major site of TSH receptor antibody and those in whom additional sites of TSH receptor antibody synthesis exist.

ISSN:0891-6934    

DOI:10.3109/08916939008995732

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

EBV transformable peripheral blood B cells secreting antibodies reactive with cell surface antigens present on two indicator human leukemia cell lines, NALM1 and U937, were studied. Oligoclonal EBV trans-formants from patients with a variety of diseases were frequently found to produce cell surface reactive antibodies. Antibody secreting transformants could also, although less frequently, be readily cultured from the PBM of normal volunteers, and represented, by limiting dilution, 1 out of 113 transformable B cells. CD8 antibody had no effect on the frequency of antibody producing B cells, but depletion of CD8 + cells by immunomagnetic methods prior to transformation significantly (P<0.05) increased the recovery of antibody secreting B cells to 1/33. Readdition of magnetically depleted cells did not significantly inhibit the transformation of these B cells. During the acute and recovery phases of some infections increasing numbers of these transformable antibody producing B cells appear in the circulation. The majority of antibodies produced were of the IgM class, although IgG antibodies were also detected. IgM antibody producing transformants were tested and some were found to react with autologous and allogeneic normal lymphocytes. These results lend support to the notion that B cells capable of secreting cell surface reactive antibodies, a proportion of which are autoreactive, are present in the normal repertoire of healthy adults, and that these cells are under active regulation by CD8 + cells.

ISSN:0891-6934    

DOI:10.3109/08916939008995733

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

We present the results of a study of the physical, haematological and serological features of the progress of the SLE-like syndrome in MRL/Mp-lpr/lpr and (NZB x NZW)F1 mice. As part of this study, we have analysed the IEF spectrotypes of anti-ssDNA antibodies in the sera of these mice and shown that the anti-ssDNA response is clonally restricted, as we have previously shown in a mouse chimaera model and in human SLE. Sequential qualitative and quantitative analysis of anti-ssDNA clonotypes has revealed that the lupus mouse anti-ssDNA clones are relatively short lived, having a lifespan of only 6 to 8 weeks, contrasting sharply with the much longer lifespan previously reported for a mouse anti-DNP-secreting clone and the exceptionally long lifespan of most anti-ssDNA-secreting clones of SLE patients. The implications of these observations for our understanding of the regulation of the autoimmune response are discussed.

ISSN:0891-6934    

DOI:10.3109/08916939008995734

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor