摘要:

To determine the influence of adjuvant on the induction of antibodies to thyrotropin receptor (TSHR), we immunized BALB/c mice with a extracellular domain of the TSHR (ETSHR) protein in complete Freund's adjuvant (CFA), Titer Max (TM) and Gerbu. Similarly, control groups of mice were immunized with bovine serum albumin (BSA) in each of the different adjuvants. As determined by ELISA, ETSHR given along with CFA elicited high titers of antibodies to ETSHR which were mainly restricted to the IgGI subclass, Mice immunized with ETSHR in TM also developed high titers of anti-EI'SHR antibodies but had higher levels of both IgG1 and IgC2a. However, immunization with ETSHR in Gerbu resulted in low titers of antibodies, restricted to IgGI subclass. Immunization of mice with BSA in each of the three adjuvants induced higher antibody titers to BSA. The subclass of antibodies in mice immunized with BSA in CFA and TM were predominantly IgG1 and IgC2a with lower levels of IgG2b, whereas in Gerbu treated group, antibody to BSA was restricted to IgG1 subclass. Analysis of specificity of antibodies against ETSHR, in mice immunized with ETSHR, revealed that irrespective of the adjuvant used, the dominant reactivity was against peptide I (AA 22–41) with weaker reactivity against several other peptides. The only exception was in mice immunized with ETSHR in TM which also showed significant reactivity against peptide 23 (AA 352–371). Mice immunized with the ETSHR in CFA or in TM showed elevated levels of serum TSH binding inhibitory immphoglobulins (TBII). However, mice immunized with ETSHR in Gerbu, which had lower titers of antibodies to ETSHR, showed normal TBII levels. These studies showed that adjuvant composition could influence the titer, subclass and fine specificity of antibodies to ETSHR which in turn could affect the development of TBII activity.

ISSN:0891-6934    

DOI:10.3109/08916939608994713

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

A comparative study of tyrosine phosphorylation was performed on peripheral blood lymphocytes from systemic lupus erythematosus (SLE) patients and from healthy donors. Freshly isolated SLE lymphocytes presented an elevated tyrosine phosphorylation level when compared to healthy donors lymphocytes (p= 0.005). Among all phosphorylated proteins, those called pi20, pl 10, p80 and p55-p60 were more phosphorylated. The level of tyrosine phosphorylation of p120 and p110 proteins discriminated significantly (p= 0.0048, respectively,p= 0.02) between SLE patients and healthy donors.Lymphocytes from SLE patients and healthy donors were then stimulated by cross-linking T cell antigens (CD3, CD4, CD8) to further distinguish the signal transduction between normal and pathologic lymphocytes. No statistical differences in the tyrosine phosphorylation pattern, following CD4 or CD8 cross-linking, were observed between SLX patients and healthy donors lymphocytes. CD3 cross-linking induced an effect on tyrosine phosphorylation different in SLE patients versus healthy donors lymphocytes. Thus, the lymphocytes of SLE patients were refractile to anti-CD3 stimulation in comparison with the healthy donors lymphocytes. Chi-square analysis demonstrated that a significantly larger number of healthy donors responded to anti-CD3 stimulation compared to SLE patients (p= 0.03). The high frequency of tyrosine phosphorylation of p110 and p80 proteins, following CD3 stimulation, in normal versus SLE lymphocytes, suggested that these proteins could be involved in abnormal signal transduction in SLE cells.

ISSN:0891-6934    

DOI:10.3109/08916939608994714

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Isoelectric focusing (IEF) spectrotype of specific immunoglobulins has been studied as a marker for B-cell clonality. In the present study, the spectrotype of anti-La antibodies in human autoimmune sera were analyzed by newly developed IEF sandwich assay in which focused total immunoglobulin on filter papers are incubated with crude antigen followed by horse-radish peroxidase-labeled anti-La antibodies. The anti-La spectrotypes contained oligoclonal bands, the positions and patterns of which are different in each patient, suggesting the preferential expansion of limited numbers of anti-La producing B-cell clones unique to individual patients. Furthermore, the bands on anti-La spectrotype in sequentially obtained sera changed continuously, suggesting alteration in the expanding anti-La producing clones. These may reflect affinity maturation and/or diversification of the B-cell epitopes involving somatic mutation.

ISSN:0891-6934    

DOI:10.3109/08916939608994715

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Expression of CD45RB on CD4+or CD8+cells in combination with TCRVβusages (Vβ6, Vβ8.1, Vβ8.2, Vβ11 and Vβ7a) in normal mouse strains (BALB/c and C57BL/6) was compared with autoimmune-prone strains ((NZW×BXSB) F1 and MRL/1pr) at young and old ages. The frequencies, and also the numbers of CD45RB cells in CD4+T cells with various TcR repertoires was significantly less in the autoimmune-prone strains at old ages, while, in normal control strains, they remained unchanged. Furthermore, CD4+/CD45RB-cells are CD4highand CD62L (L-selectin).lowThese findings suggest that most T cells, especially CD4+T cells, in old W/BF1 and old MRL/1pr mice, were activated and this may reflect the elevation of autoantibodies and the progress of autoimmune status in aged autoimmune-prone mice. This will be discussed in relation to the progress of the autoimmune diseases.

ISSN:0891-6934    

DOI:10.3109/08916939608994716

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

We have utilized a severe combined immune-deficient (SCID) mouse adoptive transfer model to explore thein vivoimmunostimulatory effects of bacterial superantigens (SAg). B cell reconstituted SCID recipients were treated with theStaphylococcusaureus-derived toxic shock syndrome toxin (TSSI-1) alone or in conjunction with syngeneic L3T4+TSST-1-reactive Th, cells. Over several months of study, the repetitive administration of TSST-1 resulted in a prompt, transient increase in serum IgG levels. This response required both biologically active TSST-1 and Th, cells. These findings demonstrate that certain bacterial SAgs can promote Th, cell-dependent B cell activation and differentiationin vivo. These studies strengthen the analogy between SAg-mediated and allospecific Th-B cell interactions responsible for the autoimmune sequelae of graft-versus-host disease.

ISSN:0891-6934    

DOI:10.3109/08916939608994717

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Little is known of the genetic factors that may contribute to the development of chronic idiopathic thrombocytopenic purpura (cITP). We have previously shown that a developmentally regulated Vh gene (Humhv 3005) is absent in 10/41 (24940) of patients with systemic lupus erythematosus while it is absent in only 7/88 (8%) of normal controls. This finding suggests that a homozygous deletion of an Ig variable (V) gene may alter the immune system and thus predispose the host to an autoimmune disorder. We have analyzed the same gene in 44 patients with cITP and found that Humhv3005 and like genes were absent in a higher percentage of patients (14 of 44, 31.8940) than they were absent in either normals (7/88, 8%, p = 0.002) or thrombocytopenic patients without cITP (6/53,11.3940, p = 0.042); the hv3005 deletion frequency in the latter group did not differ from that in normals (p = 0.74). These data suggest that deletions of Humhv3005 and/or highly homologous Vh genes may predispose individuals to the development of cITP, and may contribute toward production of pathogenic antiplatelet antibodies.

ISSN:0891-6934    

DOI:10.3109/08916939608994718

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Although systemic lupus erythematosus (SLE) is a representative collagen disease, the etiology remains unclear. However, both genetic and environmental factors seem to be involved. Based on serological studies, associations between certain human leukocyte antigens and many autoimmune diseases have long been suggested. Regarding the genetic aspects of SLE, the HLA haplotype is regarded as a potentially important factor, although its role remains controversial. Recently, we examined three family members who had SLE with an identical HLA haplotype.

ISSN:0891-6934    

DOI:10.3109/08916939608994719

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939608994720

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor