ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02884.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02885.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02886.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Recently we showed that not only homozygous MRL lpr/lpr mice but also heterozygous MRL +/lpr mice display defective antigen‐ and mitogen‐driven T‐cell responses as well as polyclonal B‐cell activation compared with congeneic MRL +/+ mice. In this study we examined die impact of the heterozygous lpr gene on organ pathology in kidneys, joints, and salivary glands, as well as serum levels of immunoglobulins and autoantibodies in young and old MRL mice. Only 1 out of 17 heterozygous lpr‐bearing MRL mice developed clinically overt renal disease with significant proteinuria and haematuria during the first year of life. However, examination of Ig and C3 deposits in glomeruli of kidneys from these mice revealed that the expression of the heterozygous lpr gene in MRL mice accelerates glomerulonephritis in addition, histological examination of the submandibular salivary glands showed an increased focus score in heterozygous MRL mice at 4–5 months of age compared with that of matched congeneic +/+ mice. In contrast, no signs of arthropathy were registered in the heterozygous lpr‐bearing MRL mice. Heterozygous MRL mice displayed an expanding lymphoid system as evaluated by significantly increased spleen and lymph node weights com pared with those of matched MRL +/+ mice. Further evidence for immunomodulatory properties of the heterozygous lpr gene was obtained when analysing serum levels of IgG, IgM, and autoantibodies. Thus, heterozygous MRL +/lpr mice produced significantly higher levels of both Ig and autoantibodies than matched MRL +/+ mice. We conclude that the expression of the heterozygous lpr gene in MRL mice results in acceleration of the autoimmune process, giving rise to precocious cli

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02887.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The aim of this study was to examine whether the unresponsiveness of MHC class I‐negative subclones of the EL‐4 thymoma lo CD3 cross‐linking can be restored by transfection of class I genes into the H‐2‐negative cells. Cell activation experiments with selected MHC class I‐negative subclones and H‐2b‐and H‐2Ld‐positive transfectants showed that these cells are equally capable of secreting interleukin 2 (IL‐2) after exposure to the phorbol ester phorbol 12‐mvristalc 13‐acetale (PMA) and ionomycin. In contrast, only the parental H‐2‐positive EL4 cells are capable of responding to treatment with immobilized anti‐CD3 antibody with IL‐2 secretion and IL‐2 receptor expression. Measurements of intracellular free Ca2+(Ca2+i) following anti‐CD3 antibody‐induced cross‐linking of parental EL4 cells and H‐2‐negativeand H‐2bgene‐transfected subclones showed that the parental cells and two of the class I transfectants, one H‐2‐positiveand one H‐2‐negative. responded with a slow rise in Ca2+,. whereas one H‐2‐positive transfected cell clone was completely refractory to CD3 cross‐linking. Modulation experiments using parental EL 4 cells, H‐2‐negative subclones and H‐2‐positive transfectants demonstrated that the CD3 and class I molecules of these different cells are modulated to the same extent after exposure lo specific antibodies. The present findings thus indicate that the unresponsiveness of H‐2‐negative EL4 subclone cells not CD3 cross‐lin

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02888.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Human α1‐m microglobulin (α1‐m), a low molecular weight plasma protein, was found to exert mitogenic effects on mouse lymphocytes from lymph nodes and spleen. The stimulatory effects appeared lo be strain‐restricted: α1‐m induced a varying degree of proliferation of lymphocytes from three strains, whereas one strain responded poorly. Experiments with lymphocyte subpopulations showed only weak stimulatory effects of α1‐m on purified T and B lymphocytes cultivated alone. The addition of mitomycin‐treated cells of the other subpopulation could not restore the proliferative responses in either T or B lymphocytes. Strong stimulations were recorded only when both T and B lymphocytes were present, indicating that the T and B lymphocytes cooperate to achieve the proliferation However, FACS studies on cultured splenocytes indicated (hat the proliferating cells are predominantly B lymphocytes. These data extend our earlier findings of a mitogenic effect of α1‐m on guinea pig lymphocytes. Furthermore. results were obtained indicating the presence of a receptor on mononuclear cells. Iodine‐labelled α1‐m was bound lo mononuclear cells prepared from spleens, and the binding could be blocked by an excess of non‐labelled α1‐m. Scatchard plotting of the data gave an equilibrium constant of 0.7 × 105/M for the binding between α 1‐m and the receptor. Together with the documented inhibitory activity of α1‐m on antigen‐driven proliferation of lymphocytes, these results sugg

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02889.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The purpose of the present study was to analyse and correlate variations in lymphocyte sensitivity to, and binding of, ciclosporin (CsA) in vitro. Peripheral blood lymphocytes from healthy individuals were harvested over a 5‐week period and activated with purified protein derivative (PPD) or alloantigens in the presence or absence of CsA [I μg/ml). Sensitivity to CsA was expressed as the ability of the drug to suppress cell proliferation ([3H]thymidine incorporation) and high‐affinity imerleukin‐2 receptor (IL‐2R) expression. Binding capacity was tested in a [3H]CsA binding assay.A significant variability in both sensitivity and binding capacity was recorded between individuals (P<0.001) There was no correlation between high sensitivity and high binding capacity. The intraindividual day‐to‐day variability did not differ significantly from the experimental (intra‐ and interassay) variability. The CsA‐induced suppression of high‐affinity IL‐2R expression varied between 57.1 and 98.9%, while suppression of [3H]thymidine incorporation varied between 81.0 and 97.4% Specific binding of 10 nM[3H]CsA at 37° C varied

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02890.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Interleukin l (1L‐I) exerts both stimulatory and inhibitor) (cytotoxic) effects on insulin producing βcells in isolated pancreatic islets. Since alteration in ion fluxes is crucial for endocrine cell activation and is a denominator of cell death, and since IL‐1 was recently shown to increase the total sodium content in a murine pre‐B‐lymphocyte cell line, we investigated the effect of recombinant human IL‐lβ (rhIL‐1β) on the cytosolic tree sodium concentration (Na+) in rat islets, furthermore, long‐term rhIL‐1βeffects on islet cell function were studied during exposure of islets to amiloride. a blocker of the plasma membrane Na+/H+exchange. One hour of islet exposure to 60 U/ml of rhIL‐lβ caused a threefold increase in I Na+. in islet cells, and this effect was abolished by deplelion of extracellular sodium. Blockade of Na+/H+exchange with amiloride abolished the inhibitory effect of rhIL‐1β Son insulin release. In conclusion. rhIL‐lβwas found to increase sodium influx in pancreatic islet cells. This might underlie the widespread effects of rhIL‐lβ on β‐cell function and morphology, possibly related to IL‐l

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02891.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02892.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02893.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY