摘要:

AbstractHighly purified populations of intraepithelial lymphocytes (IEL) were obtained from the murine small intestine. We found that 84% of IEL expressed Lyt‐2 and that 45‐55% possessed the unique phenotype, Thy‐1−, Lyt‐1‐, Lyt‐2+. Sixty percent of IEL had granules in their cytoplasm and thus resembled the large granulated lymphocytes associated with natural killer (NK) activity. However, less than 15% of IEL had NK activity in a 6‐h assay. This activity resided in a subpopulation of Lyt‐2‐ lymphocytes, leaving a large population of Thy‐1−, Lyt‐1−, Lyt‐2+granulated cells (45‐55% of IEL) with unknown function. Sensitive radioenzymic assays for histamine showed that IEL from healthy CBA mice do not contain this amine. IgE‐binding assays revealed that IEL, unlike mast cells, do not carry high‐affinity receptors for IgE. Thus, only a small percentage of granulated IEL (<15%) possess NK activity, whereas 45‐55% of IEL have granules, lack typical characteristics of mast cells, express the unique antigenic phenotype, Thy‐1−

ISSN:0014-2980    

DOI:10.1002/eji.1830150302

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractHighly enriched preparations of intraepithelial lymphocytes (IEL) containing a large subpopulation of granulated cells were isolated from the murine small intestinal mucosa. We cultured IEL in media containing interleukin 2 (growth media conditioned with 20% concanavalin A supernatant; Con ACM) or mast cell growth factor(s) (growth media conditioned with 40% WEHI‐3 supernatant; WEHI CM) and compared the physical and functional properties of the cultured cells to freshly isolated IEL. IEL cultured in Con A CM developed enhanced cytotoxicity against YAC‐1, compared to freshly isolated IEL, and spontaneous cytotoxicity for P815 targets. Most of these cultured cells were Thy‐1+Lyt‐1−Lyt‐2+, and contained cyto‐ plasmic granules similar to those seen in electron photomicrographs of other cytotoxic cell populations.IEL cultured in WEHI CM gave rise to cells that morphologically resembled mast cells. Unlike freshly isolated IEL, the cells stained metachromatically, contained 20C‐450 ng of histamine/106cells and expressed high‐affinity receptors for IgE. Our data clearly show that, although IEL do not themselves have physical characteristics of mast cells, they do contain mast cell precursors. In addition, IEL grown in the presence of T cell growth factors give rise to an activated cytotoxic cell population which is mostly granulated and T

ISSN:0014-2980    

DOI:10.1002/eji.1830150303

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractThe expression of Fcγ2breceptors and receptor‐mediated arachidonic acid metabolism by murine peritoneal macrophages was examinedin vitro.The expression of Fcγ2breceptors was found to increase progressively with time in culture and this increase was dependent on protein synthesis and glycosylation. The increase in Fcγ2breceptor expression was inhibited by hydrocortisone and by BW755C, an inhibitor of both the lipoxygenase and cyclo‐oxygenase pathways of arachidonic acid metabolism. Inhibition by BW755C was found to be reversed in the presence of exogenous leukotriene D4. In contrast, selective inhibition of the cyclo‐oxygenase pathway by indomethacin enhanced the increase in receptor expression. This enhancement was only partially reversed by exogenous prostaglandin (PG)E2. Interaction of the FCγ2breceptor with ligand in the form of erythrocytes specifically sensitized with IgGzbresulted in the release and subsequent metabolism of arachidonic acid. PGE2was found to be the principal product. Occupation of the Fcγ2areceptor did not result in arachidonic acid release. Down regulation of Fcγ2breceptor expression produced a commensurate reduction in receptor‐mediated phospholipase activity measured by arachidonic acid release. Macrophages cultured for 24 h in the presence of fetal calf serum without additional stimuli produced substantial amounts of eicosanoids. PGI2was the principal product. Taken together these data demonstrate a potential feedback regulation of receptor‐triggered arachidonic acid metabolism by eicosanoids acting at the level of Fcγ2brec

ISSN:0014-2980    

DOI:10.1002/eji.1830150304

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractThe T cell‐mediated Cytotoxic response against autologous cells modified with the sulfhydryl reagent I‐AED (N‐iodoacetyl‐N′‐(5‐sulfonic‐l‐naphthyl) ethylene diamine) is hapten specific and H‐2 restricted (Levy, R. B., Shearer, G. M., Richardson, J. C. and Henkart, P. A.,J. Immunol.1981.127: 523). We have produced a monoclonal antibody (V‐6‐3, IgM) which binds to AED‐modified cells and proteins. Competition experiments by free hapten indicated that the binding was AED specific. The effect of the mAb on AED‐specific cytotoxic T cell recognition at the effector and induction stage has been examined. Anti‐AED mAb inhibited the cell‐mediated lysis of some but not all AED‐specific, H‐2b‐restricted long‐term cytotoxic T cell clones and of bulk‐cultured C57BL/6 anti‐AED‐self effector cells. This blocking was not due to nonspecific agglutination of targets since lysis of AED‐modified target cells by alloreactive effector cells was not affected by this mAb under comparable conditions. Furthermore anti‐AED mAb specifically inhibited the antigen‐induced proliferation of AED‐specific long‐term cytotoxic T cell clones and the generation of AED‐specific cytotoxic effector cells in secondary cultures. This monoclonal anti‐AED antibody bound to cells modified by the recently described aminoreactive reagent AED‐NH2(Takai, Y., Mizuochi, H., Fujiwava, H. and Hamaoka, T.,J. Immunol.1984.132: 57); these same target cells were,

ISSN:0014-2980    

DOI:10.1002/eji.1830150305

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractPlasma cells containing intracellular inclusions of immunoglobulin (Russell bodies) are known as Mott cells, and are found in large numbers in lymphoid organs in autoimmune mice. Hybridoma technique was used to produce cell lines of this phenotype by fusing spleen cells from a NZB mouse with a nonproducing hybridoma cell line (Sp2/0‐Ag14), allowing us to carry out studies of this cell type at the biochemical level. Ultrastructurally the inclusions were distended cisternae of rough endoplasmic reticulum, suggesting a block in the secretory pathway of the cells. Biosynthetic labeling studies confirmed that these cell lines have either a complete or partial block of secretion of immunoglobulin, possibly due to an abnormal light chai

ISSN:0014-2980    

DOI:10.1002/eji.1830150306

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractA long‐chain linear mono‐benzylpenicilloyl (BPO) oligoamide and a succinoylated mono‐BPO decalysine were tested in BALB/c mice for suppression of IgE and IgG1antibody formation. Both compounds were available with either a free C‐terminal end or were C‐terminally linked to a hydrophobic 3β‐cholestanyl residue. Only the sterol‐containing derivatives suppressed hapten‐specific IgE and IgG1responses. Substantial suppression was obtained when the compountds were administered before primary or secondary, but not later immunizations.In an adoptive cell transfer experiment, spleen cells from tolerized animals actively suppressed anti‐BPO IgE antibody formation of immune spleen cells. This effect was reversed by pretreatment of the tolerized spleen cells with anti‐Lyt‐2.2 antibody plus complement.The requirement for macrophages in the induction of T suppressor cells was demonstrated by injecting antigen‐pulsed macrophages into naive recipients; upon immunization, only mice treated with tolerogen‐pulsed macrophages showed suppressed anti‐BPO IgE responses. It is suggested that lipid modification of antigens alters their processing and presentation by macrophages in a manner that leads to the induction of T suppressor cells.Injection of the cholestanyl derivatives into passively sensitized guinea pigs elicited anaphylactic reactions. By immune precipitation analysis and molecular weight estimation, these derivatives were shown to form micelles in aqueous solution. Therefore, the anaphylactic response appeared to be due to their beha

ISSN:0014-2980    

DOI:10.1002/eji.1830150307

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractLactic dehydrogenase elevating virus (LDV) was found to selectively stimulate IgG2asynthesis in infected mice. Within one week after infection, the production of IgG2aincreased nearly 50‐fold whereas that of IgM, IgA, IgGland IgG3remained virtually unchanged. IgG2bsynthesis was also enhanced but to a lesser extent. Several observations suggested that this stimulation of IgG2production resulted from a polyclonal B cell activation: (a) the isoelectric focusing patterns of IgG2a, before and after LDV infection were exactly the same, (b) the frequency of clones with anti‐LDV activity in hybridoma collections derived from infected mice was extremely low (less than 4/ 1000) and (c) the proliferative response elicited by LDV in unsensitized animals was comparable with that induced by lipopolysaccharide. The effect of LDV on immunoglobulin synthesis was drastically reduced in nude mice but was not affected by the X‐linked B lymphocyte defect of animals carrying thexidmut

ISSN:0014-2980    

DOI:10.1002/eji.1830150308

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractThe accessory function (AF) of various B cell lines has been investigated by studying their ability to replace monocytes inducing the proliferation of highly purified T lymphocytes in the presence of phytohemagglutinin. AF could be exerted by B cells from different origin, including Epstein‐Barr virus (EBV) transformed lymphoblas‐toid cell lines (LCL), Burkitt's lymphoma (BL)‐derived lines, either EBV‐positive or not, pre‐B and B leukemias and lymphomas. The EBV‐converted BJAB‐B95 BL cells could exert an AF as efficient as BJAB cells, their EBV‐negative counterparts, which demonstrates that EBV itself does not play any role in this function. The HLA‐DR antigen‐negative BL‐K562 hybrids PUTKO and DUTKO, T51.4.1.6 cells which derived from an HLA‐DR‐negative variant of the T51 LCL and 721.84.5 cells from a mutagenically dissected HLA‐DR‐negative clone of the 721 LCL, also exerted very efficient AF. 721 LCL, PUTKO and DUTKO hybrids could produce interleukin 1 activity when triggered with 12‐0‐tetradecanoyl‐phorbol 13‐acetate (TPA). Furthermore, addition of anti‐DR monoclonal antibodies which blocked completely the AF of the B cell lines in mixed lymphocyte‐tumor cell reaction did not affect the mitogen‐triggered AF exerted by the same B cell lines. The induction of cellular differentiation with TPA markedly reduced the AF exerted by all B cell lines studied as well as by the hybrid cells DUTKO. By contrast, the PUTKO hybrid was unsensitive to sodium butyrate and TPA treatments, which were unable to abrogate its AF. Taken together, these data indicate that the AF in mitogen‐induced T lymphocyte responses is dependent upon some precise maturational stages of accessory cells and HLA‐DR antigen expression is not required

ISSN:0014-2980    

DOI:10.1002/eji.1830150309

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractThe autologous mixed lymphocyte reaction (AMLR) represents the activation, proliferation and differentiation of T cells in response to signals from autologous non‐T cells. Upon stimulation by autologous non‐T cells, OKT4+cells produce interleukin 2 (IL2); cells contained within both OKT4+and OKT8+cell populations can also be activated by autologous non‐T cells to become sensitive to IL2. Once these activated OKT4+and OKT8+cells are exposed to IL2 produced by OKT4+cells, they will proliferate and go on to differentiate into effector cells.Patients with systemic lupus erythematosus (SLE) have a defect in the AMLR. The ability of OKT4+cells to produce IL 2 in the AMLR is impaired. Upon triggering with autologous non‐T cells, their OKT8+cells become sensitive to proliferative signals of IL2; however, their OKT4+cells fail to express IL2 receptors. These defects are a consistent feature in patients with SLE. AMLR‐induced immunologic processes which require cell interactions between OKT4+cell subpopulations are not correct‐ able even by the addition of normal IL2. However, the immunologic processes medi ated through OKT4+‐OKT8+cell interactions can be corrected with normal 1L2. The latter finding suggests that the partial correction of the AMLR‐induced immunologic processes with IL 2 might lead to suppressed B cell hyperactivity of pa

ISSN:0014-2980    

DOI:10.1002/eji.1830150310

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY

摘要:

AbstractPolyclonal anti‐human thyroglobulin (hTgb) antibodies (Ab) were purified from sera of rabbits immunized with human thyroglobulin, normal humans and patients suffering from Graves' disease, Hashimoto's thyroiditis and thyroid carcinoma. The avidity of the various Ab preparations for hTgb ranged from 0.3 × 1010−2.2 × 1010M−1. By using well characterized mouse monoclonal antibodies (mAb) directed against hTgb, it was shown that the fine specificities of induced anti‐hTgb Ab in rabbits, natural Ab in normal subjects and autoantibodies in diseased patients were similar; however, they differed from that of rabbit anti‐bovine and anti‐porcine thyroglobulin Ab which were able to inhibit the hTgb binding of only a few of the mAb. Anti‐hTgb in rabbits and in patients with thyroid carcinoma varied from those in normal subjects only by uniformly elevated serum titers. In contrast, patients with Graves' disease and Hashimoto's thyroiditis showed an increased concentration essentially restricted to Ab reacting with few of the antigenic determinants recognized by the mAb. Our data suggest that the repertoire of anti‐hTgb Ab is similar in mouse, rabbit and human. Furthermore, the finding of identical fine specificities for anti‐hTgb Ab in normal and pathological conditions implies that autoantibodies are produced in normal subjects and held to a low level by regulatory processes which fail with respect to selected epitopes in

ISSN:0014-2980    

DOI:10.1002/eji.1830150311

出版商:WILEY‐VCH Verlag GmbH    

年代:1985

数据来源: WILEY