ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb01066.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

We have investigated the ability of human recombinant gamma interferon (IFN‐γ) to induce functional differentiation in three human myclomonocytic cell lines U937, RC2A, and ML‐2. Treatment with IFN‐γ induced natural killer (NK) cell like cytotoxicity against K‐562 cells in ML‐2 and RC2A but not in U937. U937 and RC2A displayed a spontaneous antibodydependent cell‐mediated cytotoxicity (ADCC), which against nucleated target cells was significantly increased in U937 but not in RC2A after treatment with IFN‐γ. ML‐2 did not display ADCC against nucleated targets either before or after IFN‐γ treatment, but lysed efficiently antibody‐coated erythrocytes. All three cell lines displayed enhanced ADCC against erythrocytes after IFN‐γ treatment. Spontaneous phagocytosis of erythrocytes was seen in U937, and this was enhanced by IFN‐γ treatment, while ML‐2 and RC2A were phagocytically inactive before and after treatment with IFN‐γ. The differentiated functions induced by IFN‐γ treatment in this panel of phenotypically closely related cell lines offers an interesting model for further studies on the IFN‐γ regulated gene expression. Moreover, the increased cytolytic capacity after exposure to IFN‐γ might have implications on the use of IFN‐y for treatment of myelomonocytic malignancies. In such cases, IFN‐γ migh

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb01067.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

We have previously demonstrated that monoclunal anti‐I‐A/E antibodies inhibit B‐cell responses lolipupolysaccharide (LPS). In the present report, the inhibitory effects were shown to be carried out directly on B cells. and to be totally independent of the LPS concentration used, thereby showing that antibodies do not mediate their effect through blocking of accessory cells or steric hindrance of LPS‐receptors. Of the three different phases in B‐cell activation/ induction, proliferation, and maturation, induction was shown to be the most sensitive to inhibition by anti‐I‐A/E antibodies. Thus, kinetic studies showed that anti‐I‐A/E antibodies are only inhibitory for the first 16 h of LPS activation, after which B cells can no longer be inhibited by these antibodies. Class II MHC molecules appear, therefore, to be part of a membrane molecular complex which regulates delivery of activation signals to resting B ceils. Since it was also shown that this time period corresponds approximately to the time required for B cells to express functional reaciivity to growth factors, we suggest that anti‐I‐A/E antibodies act on resting B lymphocytes to inhibit mitogen‐dependent induction of gro

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb01068.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Twelve insulin‐dependent diabetes mellitus (IDDM) patients and healthy controls, who all carried the serologically defined DR3 and DR4 antigens, were compared with respect to other HLA polymorphisms. No significant differences between patients and controls were found by typing for HLA‐Dw determinants by homozygous cell typing, nor by studies of their genomic DRβ polymorphism using different restriction enzymes. In contrast, certain DR4‐associated genomic DQβ fragments had a significantly different distribution among the IDDM patients than among the controls. Furthermore, when the distribution of all DQβ‐specific fragments which demonstrated polymorphism in our material was taken into account, nine of the 12 DR3, 4 IDDM patients demonstrated a similar DQβ polymorphism compared with only two out of the 12 DR3, 4 controls (P=0.006; corrected P=0.037). Cells from patients and controls who demonstrated this IDDM‐associated DQβ polymorphism stimulated each other significantly Aless in reciprocal MLC tests, compared with the responses seen when their cells were confronted with cells from the DR3, 4 individuals with other genomic DQ

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb01069.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

The macrophage‐stimulating properties of some structurally related polysaccharides were studied in vitro. When the polysaccharides were presented to the macrophages in a sterically fixed form, i.e. as microparticles, they induced the release of interleukin 1 (IL‐1) from the macrophages. Microparticulate 1.3‐β‐glucan (curdlan) induced nonspecific macrophage mediated tumour cell killing while l.4‐α‐glucan (starch), 1.6‐α‐glucan (dextran), and 1.6‐α‐mannan were without effect. The corresponding soluble polysaccharides did not stimulate the macrophages. Kinetic studies showed that although IL‐1 was released immediately after stimulation, the macrophages needed a time lag of several days to develop tumour cytotoxicity. The development of cytotoxicity paralleled binding of tumour cells to the macrophages. Resident and inflammatory peritoneal macrophages showed differences in their responses to the polysaccharides. Stationary, resident peritoneal macrophages stimulated by macroparticles secreted high levels of IL‐1 but expressed a low cytotoxic activity, while newly recruited inflammatory macrophages released lower levels of IL‐1 but readily killed the tumour cells. The influence of cyclo‐oxygenase products on the IL‐1 release and macrophage cytotoxicity was also investigated. When cyclo‐oxygenase was blocked with indomethacin, a significantly higher release of IL‐1, and then an increased cytotoxicity, were obtained with 1.3‐β‐glucan stimulated macrophages. The results suggest that microparticulate polysaccharides may be useful for studies on the induction of macrophage differentiation and also for studies on nonspecific cell

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb01070.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

T‐helper cells (ThC) play an important role in the induction of both cytotoxic T‐cell responses and B‐cell responses against the grafted organ. Furthermore, ThC alone are capable of causing graft rejection in T cell‐deprived mice and rats. In view of these observations we found it important to analyse the frequency and functions of donor‐specific ThC in the allograt and in the recipient lymphoid system during the course of acute renal allograft rejection. A limiting dilution assay was developed which, due to the absence of exogenous interleukin 2 (IL‐2) and the low numbers of stimulator cells used, appears to be highly selective for the proliferation of specific ThC. Kidney transplants were performed from LBN (RT1n) to congenic Lewis (RT11) sirain differing in major histocompatibilily complex (MHC) only. The inflammatory (white) cells were recovered from the graft, and blood and recipient spleen and the frequency of RT1n‐ responding ThC were determined at different times after transplantation. In the kidney graft itself, the frequency of ThC responding to RT1nMHC antigens was 1:3000 on day 2 and increased to l:670–1320 at the peak of inflammation. In the spleen, the frequency increased from l:l000 on day 0 to 1:200 on day 8, and remained high even after the graft was rejected. In the blood, the frequency stayed at the 1:400–1:800 level, and increased to 1:200 only after the graft had been completely destroyed. Individual ThC clones deriving from limited dilution assays of kidney and spleen cells were recovered and expanded with irradiated donor cells without IL‐2 and finally with exogenous IL‐2 only. All clones showed the T‐helper (W3/25) phenolype, seven out of eight tested clones showed a specific anamnestic response lo RT1nalloantigens and no response to RT11or RT1ain a secondary MLC, 12 out of 12 clones produced IL‐2 and 11 out of 11 clones produced gamma interferon upon re‐stimulation with relevant allogeneic cells, and eight out of ten clones collaborated with syngeneic B cells for Ig synthesis, indicating that they were indeed derived from specific ThC and/or from their precursors. Taken together, the results demonstrate that specific ThC and/or their precursors represent only a very small minority in the graft‐infiltrating inflammatory population. This makes it most unlikely that ihe ThC themselves are responsible for graft destruction; the results indicate rather that a major role of ThC in situ may be instruction of immunologically specific and nonspecif

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb01071.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Spontaneous and pokeweed mitogen‐induced production of specific autoantibodies were studied in cultures of peripheral blood mononuclear cells from patients with different clinical stages of myasThenia gravis. Receptor antibody‐related idiotypes and anti‐idiotypic antibodies were defined by binding to mouse monoclonal anti‐idiotypic and anti‐receptor antibodies, respectively. Patients with severe disease had a more complete spectrum of idiotypes in serum, and cells from such patients spontaneously produced more antibody species and higher concentration of both idiotypes and anti‐idiotypes than patients with mild disease. The frequencies of antibody specificities in tissue culture supernatants more closely reflected disease activity than those in serum. Tissue culture for the study of different species of autoantibodies has proved to be a useful tool for monitoring the disease and the effects o

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb01072.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Serum amyloid P comptinent (SAP), a normal human plasma glycoprotein. was found in a solid phase ELISA to have Ca2+‐dependent binding for keyhole limpet haemocyanin (KLH), pectic acid, trinitrophenylated (TNP) maeromolecules, and plastic surfaces. The binding U) TNPKLH was used to develop a sensitive ELISA. The binding of SAP to the ligands mentioned was inhibited by EDTA, KLH, pectic acid, TNP‐conjugated macromolecules (bovine serum albumin, polyacrylhydrazide), and p‐nitrophenylarsonic acid, Underivatized and DNP‐conjugated macromolecules did not inhibit the SAP binding; arsenilic acid, picric acid, and dinitrophenyl were weak inhibitors. SAP bound to TNP‐agarose was eluated by either EDTA or p‐nitrophenylarsonic acid. Thus, a unique region of SAP is responsible for the polyspecific binding. We suggest that the polyspecific binding of SAP takes place through a Ca2+bridge: half of the metal coordination sphere is occupied by SAP. with the other half available to interact with m

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb01073.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Human polymorphonuclear granulocytes (PMN) metabolize exogenous [3H]leukotriene B4 (LTB4) into 20‐hydroxy‐ and 20‐carboxy‐[3H]LTB4. The conversion was enhanced at acidic pH values (pH 6.0–7.0). Sonication of purified PMN and subcellular fractionation by differential centrifugation showed that major LTB4‐hydroxylase activity was associated with the microsomal fraction (105,000 g pellet). In contrast to intact cells. LTB4‐hydroxylase activity within the microsomal fraction revealed optimal activity at neutral pH and was inhibited by a wide range of divalent cations. There was a strict requirement for the presence of suitable electron donors such as NADPH, Heterocyclic nitrogenous bases, such as imidazole and pyridine, inhibited the LTB4, conversion induced by intact PMN as well as by their microsomes. These observations combined with the spectrophotometric analysis (carbon monoxide dithionite‐reduced difference spectrum) supported the assumption that LTB4‐hydroxylase resembled a cytochrome P‐450 enzyme. The LTB4‐hydroxylase within human PMN was not identical with the cytochrome P‐450 of rat liver; hepatic microsomes only showed mi

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb01074.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Human T‐lymphocyte clones specific for antigenic components of purified protein derivative (PPD) of tuberculin were generated by limiting dilution using in vilro PPD‐activated peripheral blood mononuclear cells from a single donor. The HLA restriction specificity of eight clones that were cytotoxic against autologous PPD‐pulsed monocyte targets, was examined against a panel of allogeneic PPD pulsed targets, In agreement with our findings with bulk‐expanded PPD‐reactive cytotoxic T lymphocytes, all clones were restricted by HLA class II antigens: seven by HLA‐DR 2 and one by HLA‐DRwlO‐the other HLA‐DR antigen of the donor. All clones were CD3+, CD44, CD8‐. One clone exhibited, in addition to HLA‐DR2 restriction, unrestricted cytotoxic alloreactivity against HLA‐DR1. In monoclonal antibody‐blocking experiments the latter clone was the only one that was blocked. Its lytic ability was abolished by two monoclonal antibodies against monomorphie HLA DR determinants. The antigen specificity of the clones was studied by using autologous monocyte targets pulsed with antigens prepared from a range of different mycobacterial species. All seven HLA‐DR2‐restricted clones reacted with the majority of antigens tested. In contrast, the HLA‐DRwlO‐restricted clone reacted exclusiv

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb01075.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY