摘要:

Hie therefore, Robin, overcast the night; The starry welkin cover thou anon With drooping fog as black as Acheron; And lead these testy rivals so astray, As one come not within another's way.William Shakespeare, A Midsummer Night's DreamAct III, Scene II

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02842.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

NcoI restriction fragment length polymorphism (RFLP) of the tumour necrosis factor B (TNFB) gene gives two allelic fragments of 5.5 and 10.5 kb, corresponding to the TNFB*1 and TNFB*2 alleles, respectively.The frequencies of these alleles were analysed in 121 healthy Finns and 56 Finnish couples suffering from recurrent spontaneous abortions (RSA). In the healthy Finns the frequency of TNFB*1 was 37% and that of TNFB*2 63%, of which the frequency of TNFB*1 was significantly increased compared with the Danish population. No deviation was seen between the RSA couples and the Finnish controls.TNF genes are located in major histocompalibility complex class III region close to complement (BF, C4A and CAB) genes. Some complotypes associated most often with the TNFB*1 (S01, S30, S02) and some (S31, F320) with the TNFB*2 allele in the healthy Finns.The combination of the TNFB and the C4 ‘null’ allele differed between the RSA couples and the Finnish contr

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02843.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Polyribosilribitolphosphate (PRP), the capsular polysaccharide fromHaemophilus influenzaetypeb, is a T‐cell‐independent type 2 antigen. In vitro culture of adult peripheral blood T cells with 15 μg/ml PRP leads to induction of interleukin‐2 receptor (IL‐2R) expression on up to 10% of T cells. These cells are CD4+and carry the αβ T‐cell receptor. PRP, at concentrations above 1–5 μg/ml, can also induce in vitro proliferation of both adult and neonatal T cells. We conclude that PRP acts as a human T‐cell mitogen.The in vitro proliferative response as well as IL‐2R expression was studied in T cells derived from adults after vaccination with native PRP, with PRP conjugated to a carrier protein, or with diphtheria toxoid. Vaccination with conjugated PRP decreased the doses of PRP required for in vitro induction of IL‐2R expression and T‐cell proliferation. This indicates that vaccination with PRP conjugated to a carrier protein improves the in vitro T‐cell r

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02844.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

We have sought to determine whether rheumatoid factors (RF) produced in rheumatoid arthritis (RA) were different from physiological RF produced in normal, healthy adults. RF‐secreting clones were established following Epstein Barr virus (EBV) stimulation of peripheral blood lymphocytes. Ten RF‐secreting clones were established from seven RA patients and 16 from six healthy controls. All monoclonal RF (MRF), except two in each group, were monoreactive and ten of these were shown to have low to medium affinity for IgG, Fc, irrespective of their origin. A majority (74%) of the MRF bound to protein A, indicating that genes of the VHIII family were preferentially used for synthesizing these autoantibodies. The expression of cross‐reactive idiotypes (CRI) by the MRF did not allow distinction between those derived from RA patients and controls. The VHI‐associated CRI G8 and VHIII‐associated CR1 D12 were expressed at low frequency in both panels of RF. These CRI have been shown to be expressed at high frequency in RF paraproteins. However, the idRQ idiotype was expressed within both panels of RF. A possible distinction between polyreactive and monoreactive MRF appeared to be light chain usage since all (four) polyreactive RF used λ chains while the normal κ/λ ratio was observed for monoreactive RF. The frequency of EBV‐activated cells secreting IgM bearing CRI or secreting RF was determined and showed that CRI expression occurred with a higher frequency than did RF, suggesting a dissociation between CRI expression a

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02845.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

With the aim of investigating the distribution of T cells expressing different T‐cell receptors (TCR) in the inflamed synovial tissue of rheumatoid arthritis patients, we have used the polymerase chain reaction to amplify TCR Vα and Vβ transcripts from synovial biopsies obtained by arthroscopy from patients with arthritis of variable duration. From each of nine patients a single biopsy was taken. Southern hybridization analysis of amplified products revealed extensive heterogeneity of TCR Vβ in most patients. On the other hand, restriction in Vα gene expression was seen in several patients. A highly restricted Vα repertoire was observed in all cases with arthritis of short duration. In addition, two of three samples of short duration yielded a more limited number of Vβ transcripts than the others. No conformity was, however, seen in usage of individual Vα and Vβ transcripts among the investigated patients. The present data thus demonstrate variability in synovial TCR expression between rheumatoid arthritis patients, but they also indicate a development towards greater diversity with increasing disease duration, implicating the necessity for careful choice of cases, preferentially selecting for early stages of disease, when further analysing rheumatoid synovial T cells for TCR usage as well as for antigen sp

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02846.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Recombinant interleukin‐4 (rIL‐4) caused a 65–70% reduction of the interferon‐α (IFN‐α) and ‐β production induced by Sendai virus (SV) in human peripheral blood monocytes in vitro. Significant inhibition was seen at concentrations as low as 0.1 ng/ml. The rIL‐4 also reduced levels of IFN‐α and ‐β mRNA by 60% and 67%, respectively, as well as the frequency of IFN‐α and ‐β mRNA‐containing cells by 65% and 54%, respectively. The frequency of IFN‐α/β mRNA‐containing cells was inhibited by rIL‐4 throughout the whole course of induction by SV. IL‐4 caused a shift of the grain count distribution towards less heavily labelled cells, suggesting an inhibitory effect of rIL‐4 on most IFN‐α/β mRNA‐containing cells. Antibodies to rIL‐4 did not influence the normal IFN‐α/β response induced by SV, but abolished the inhibitory effect of the rIL‐4.When rIL‐4 was added to cells 4 h after start of stimulation by SV, at which time much mRNA has accumulated but little IFN‐α/β has been secreted, no inhibition of the IFN‐α/β production by rIL‐4 was seen. IFN‐γ had only a minor reversing effect on the rIL‐4 inhibition, but if cells were precultivated in medium with or without IFN‐γ for 6 h before SV induction, rIL‐4 paradoxically enhanced the IFN‐α/β response.Our results suggest that rIL‐4 inhibits an early step of IFN‐α/β induction in monocytes, at the level either of transcription of IFN‐α/β genes or of the processing or stabil

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02847.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Monocytes produce interferon‐α (IFN‐α) and ‐β when human peripheral blood mononuclear cells (PBMCs) are stimulated in vitro by Sendai virus (SV). We found that about 70% of the IFN‐producing cells (IPCs) expressed both IFN‐α and ‐β mRNA; She rest expressed only IFN‐β mRNA. In the presence of the protein synthesis inhibitor cycloheximide(CHX), the frequency of IFN‐αmRNA containing cells, measured after 6 h, was decreased by 85–90%. Results of nuclear run‐on transcription assays showed that CHX inhibited IFN‐α gene expression. The frequency of IFN‐β mRNA‐containing cells was not reduced by CHX. Actually, a threefold increase was observed at the lower CHX concentrations. Studies on the kinetics of IFN‐α/β mRNA induction showed that CHX accelerated the appearance of IFN‐β mRNA‐containing cells, increased IFN‐β mRNA levels, and delayed the normally occurring post‐inductional decrease of IFN‐β mRNA. Unexpectedly, an initially normal or even accelerated IFN‐α mRNA response was seen in the presence of CHX during the first 3–4 h after SV stimulation. This occurred in a small proportion of the potential IPCs. However, CHX prevented the subsequent marked increase of IFN‐α mRNA levels. Preincubation of PBMCs for 6h in conditioned medium (CM) containing IFN and other cytokines prevented the CHX‐mediated inhibition of IFN‐α mRNA. Without preincubation this was not seen. The preincubation in CM caused an accelerated appearance of IFN‐α mRNA, resembling that of IFN‐β mRNA. The results suggest (that IFN‐α and ‐β genes are differentially regulated in the same monocytes, the former requ

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02848.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

In this study T‐cell receptor (TcR) β‐chain gene rearrangements of T‐cell lines prepared from multiple sites (n=92) of synovial tissue derived from both knees of a patient with rheumatoid arthritis were analysed. In the majority of T‐cell lines, dominant TcR β‐chain gene rearrangements were detected, involving Cβ1 as well as Cβ2. The dominant rearrangement patterns of T‐cell lines from different tissue fragments showed significant variability, but some of the DNA restriction fragments were shared by T‐cell lines from multiple sites in both knees. The latter observation suggests that identical T‐cell clones may be present at different sites in the synovial tissue and in different joints. However, since many T‐cell lines yielded different rearrangement patterns, these data also indicate considerable heterogeneity of T cells in the joints. Apart from theoretical implications, this TcR heterogeneity of T cells within an individual patient also has practical consequences for studies on synovial T cel

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02849.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The effect of murine IgG isotypes on the gene expression and secretion of the third component of complement (C3) has been studied using the monocytoid cell line P388DI and oil‐elicited mouse peritoneal macrophages. It is demonstrated that the binding of IgG2a and IgG2b but not IgG1 and IgG3 augments the biosynthesis of C3 both in the presence and in the absence of the phorbol ester. phorbol myristate acetate in the case of both cell types. The multifunctional cytokine inlerleukin‐6 (IL‐6) alone reveals no effect on the gene expression of C3, but increases the effectiveness of mouse IgG2a and IgG2b. Confirming the role of FcγRII, a strong up‐regulation of C3 gene expression and C3 secretion was found when macrophages were cultured with the F(ab')2; fragment of the FcγRII‐specific monoclonal ant

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02850.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The capability of elevated intracellular cyclic AM P concentration to activate IL‐l gene expression and protein production was examined in human peripheral blood monocytes. In accordance with previous studies it was observed that the transiently elevated cyclic AMP (induced either with prostaglandin E2 or with the direct adenylate cyclase activator, forskolin) was not a sufficient signal to activate IL‐l production. However, if the degradation of cyclic AMP was inhibited with isobutyl‐methyl‐xanthine (IBMX). IL‐l production was strongly activated. This prostaglandin E2 plus IBMX effect could also be mimicked with high concentrations of the cell permeant structural cyclic AMP analogue, dibutyryl cyclic AMP. The cyclic AMP4nduced IL‐l production differed in some aspects from the bacterial lipopolysaccharide‐induced IL‐l production: (1) the kinetics of both IL‐l gene expression and protein production was much slower: (2) the IL‐1β gene expression was superinducible by inhibiting the protein synthesis with cycloheximide. Thus these data suggest that prolonged elevation of cyclic AMP is alone a sufficient signal to acti

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb02851.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY