A Sulica, W H Chambers, M Manciulea, D Metes, S Corey, H Rabinowich, T L Whiteside, R B Herberman
{"title":"Divergent signal transduction pathways and effects on natural killer cell functions induced by interaction of Fc receptors with physiologic ligands or antireceptor antibodies.","authors":"A Sulica, W H Chambers, M Manciulea, D Metes, S Corey, H Rabinowich, T L Whiteside, R B Herberman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Natural killer (NK) cells express receptors that bind to the Fc portion of immunoglobulin molecules (FcR), and their function can potentially be modulated positively or negatively by such receptor:ligand interactions. This review discusses recent developments in the understanding of expression of various forms and isoforms of FcRs by NK cells, and the sequelae of binding of physiologic ligands. Particular attention is paid to the significance of FcR:Ig interactions in both activating and inactivating NK cells under various conditions.</p>","PeriodicalId":77279,"journal":{"name":"Natural immunity","volume":"14 3","pages":"123-33"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19800417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Increase in tumor necrosis factor-alpha mRNA but not perforin mRNA expression in response to two newly characterized anti-LFA-1 monoclonal antibodies.","authors":"G Hommel-Berrey, M Bochan, Z Brahmi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have generated two monoclonal antibodies (mAb), designated anti-1B11 and anti-4F9, directed to the human lymphocyte-function-associated antigen-1 (LFA-1). Indirect immunofluorescence with both mAb showed a bimodal distribution of antigen on the surface of T, natural killer (NK), and lymphokine-activated killer (LAK) cells. Neither mAb reacted with the epitopes recognized by TA1 and Mo-1 mAb on the alpha-chain of the heterodimer. Anti-1B11 and anti-4F9 immunoprecipitated polypeptide chains with molecular weights of 177 and 95 kD. Both mAb inhibited cytolytic T lymphocytes (CTL), NK, and LAK cell-mediated cytotoxicity without affecting antibody-dependent cellular cytotoxicity (ADCC). The proliferative responses of T cells to allogeneic cells were inhibited by anti-1B11 and anti-4F9, whereas the responses to phytohemagglutinin P and concanavalin A were not affected. Anti-1B11 and anti-4F9 blocked effector cell (EC)-target cell (TC) conjugate formation by 50%. Only anti-4F9 cross-reacted with LFA-1 on porcine peripheral blood lymphocytes and inhibited porcine NK, LAK, and ADCC activities. Because LFA-1 also functions at the level of signal transduction during T cell activation and we previously showed that CTL rapidly degraded perforin and tumor necrosis factor-alpha (TNF alpha) mRNA after interaction with sensitive TC, we examined the effects of the mAb on the messages for perforin and TNF alpha. Treatment of CTL with anti-1B11 and anti-4F9 induced TNF alpha message and protein levels of TNF alpha, but did not alter perforin mRNA levels.</p>","PeriodicalId":77279,"journal":{"name":"Natural immunity","volume":"13 6","pages":"301-14"},"PeriodicalIF":0.0,"publicationDate":"1994-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18892456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anti-Ly-6E.1-monoclonal-antibody-mediated augmentation of interleukin-2-dependent generation of natural killer cell activity from mouse bone marrow cells.","authors":"L Lu, R B Herberman, A B DeLeo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Studies have shown that the administration of anti-Ly-6E.1 monoclonal antibody (mAb) to tumor-bearing mice augments their T-cell-dependent functional activities, splenic natural killer (NK) cell activity, and antitumor resistance. The effect of the mAb on splenic NK cell activity resembles that of biological-response modifiers, which involves enhanced large granular lymphocyte (LGL) development in the bone marrow (BM) from pre-NK cells, and their subsequent migration and localization in peripheral organs. We analyze here the effect of anti-Ly-6E.1 mAb on the IL-2-dependent generation of NK cell activity in short-term cultures of mouse BM cells. The results indicate that an increase in the population of LGLs paralleled the mAb-mediated augmentation of IL-2-induced generation of NK cell activity in the cultures. Although pre-NK and T cells present in the BM expressed Ly-6 antigens, the augmentation of NK cell generation appears to be due to the mAb interacting with the T cells, not the pre-NK cells, resulting in increased synthesis of tumor necrosis factor-alpha, which in turn enhanced the interleukin-2-dependent development of NK cell activity.</p>","PeriodicalId":77279,"journal":{"name":"Natural immunity","volume":"13 6","pages":"315-30"},"PeriodicalIF":0.0,"publicationDate":"1994-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18892459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D Metes, C Galatiuc, I Moldovan, P A Morel, W H Chambers, A B DeLeo, H Rabinowich, R Schall, T L Whiteside, A Sulica
{"title":"Expression and function of Fc gamma RII on human natural killer cells.","authors":"D Metes, C Galatiuc, I Moldovan, P A Morel, W H Chambers, A B DeLeo, H Rabinowich, R Schall, T L Whiteside, A Sulica","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In this report, we present data on the expression and function of Fc gamma RII (CD32) by natural killer (NK) cells. Highly enriched NK cell populations were isolated from peripheral blood lymphocytes by negative selection and consisted of > or = 95% CD3-/CD56+ cells. Flow cytometric analyses with anti-CD32 monoclonal antibodies (mAbs) demonstrated that a small proportion of NK cells were recognized by mAbs IV.3 and 41H16. Two-color flow cytometric analysis indicated coexpression of the epitope on NK cells recognized by both these mAbs. Verification of expression of CD32 on NK cells was obtained by demonstrating coexpression of CD32 on either CD16+ or CD56+ cells. The CD32+/CD16+ and CD32+/CD56+ cells represented approximately 7 and 3% of the total, respectively. CD32 transcripts were identified from highly purified NK cells using reverse transcription-polymerase chain reaction with CD32-specific primers, followed by Southern blotting. Enhanced chemiluminescence-Western blot (ECL-WB) analysis of lysates of purified NK cells indicated that mAb IV.3 recognized a molecule of approximately 40 kD. The Fc gamma RII on NK cells was able to transduce intracellular signals in several types of assay. Cross-linking of anti-CD32 resulted in a mobilization of intracellular Ca2+, although to a lesser extent than that induced by cross-linking CD16. Both mAbs IV.3 and 41H16 were found to be capable of inducing reverse antibody-dependent cellular cytotoxicity against FcR+ target cells (e.g. P815). These data represent the first direct description of the expression and function of Fc gamma RII on human NK cells.</p>","PeriodicalId":77279,"journal":{"name":"Natural immunity","volume":"13 6","pages":"289-300"},"PeriodicalIF":0.0,"publicationDate":"1994-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18892457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phorbol ester tumor promoter regulation of natural antitumor antibody binding depends on protein kinase C and an intact microfilament system.","authors":"P A Sandstrom, D A Chow","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Phorbol ester tumor promoter treatment produced a biphasic effect on the binding of polyclonal whole-serum natural antibody (NAb) by L5178Y-F9 murine lymphoma cells. In vitro tumor growth in 100 ng/ml 12-O-tetradecanoylphorbol-13-acetate (TPA) produced a rapid decrease followed by a reversible and unstable increase in NAb binding detected at 4 degrees C. The latter was associated with a functional decrease in NAb binding at 37 degrees C and increases in the tumorigenic and metastatic potentials in vivo. Colchicine, cytochalasin B and sodium azide inhibited the NAb binding of TPA-treated cells, while only colchicine reduced the binding of controls, suggesting the dependence of the TPA-induced increase in NAb binding on microfilament organization and active energy production. The non-tumor-promoting, non-PKC-activating TPA analogue 4-O-Me-TPA failed to alter NAb binding, arguing against nonspecific effects of TPA. The non-tumor-promoting, PKC-activating diacylglycerol, OAG, reproduced the initial decrease in NAb binding but was unable to mimic the subsequent TPA-induced increase. The PKC inhibitor H-7, but not HA1004, could block the TPA-induced increase in NAb binding. Together the data argue that PKC activation is required for both TPA-induced changes in NAb binding but that it is not sufficient to generate the energy- and microfilament-system-dependent, unstable high-NAb-binding phenotype associated with increased tumor progression.</p>","PeriodicalId":77279,"journal":{"name":"Natural immunity","volume":"13 6","pages":"331-43"},"PeriodicalIF":0.0,"publicationDate":"1994-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18892462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of N-(4-hydroxyphenyl)-retinamide on the number and cytotoxicity of natural killer cells in vitamin-A-sufficient and -deficient rats.","authors":"Z Zhao, T Matsuura, K Popoff, A C Ross","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>N-(4-hydroxyphenyl)retinamide (4-HPR), a synthetic retinoid with anticarcinogenic activity, has been shown to lower the plasma retinol level rapidly and significantly. We reported previously that vitamin A-deficient rats (plasma retinol < 0.175 mumol/l) have a low number of natural killer (NK) cells in peripheral blood. To investigate the effects of 4-HPR on NK cell number and activity, two studies were conducted. In study 1, vitamin-A-sufficient rats were fed a 'therapeutic' dose of 4-HPR (2 mmol/kg of diet) for 30 days. Despite a low plasma retinol concentration (approximately 0.1 mumol/l), the number of NK cells was not reduced. Moreover, the NK cytolytic activity per cell was significantly elevated. White blood cell and differential counts were normal. In study 2, the biological activity of 4-HPR was examined in vitamin-A-deficient rats. Rats depleted of vitamin A were fed a diet containing 4-HPR (54.7 micrograms/g of diet) for 11 days. Vitamin-A-dependent processes including growth, hematocrit, lymphocyte count and the number of NK cells were restored. For comparison, another group of vitamin-A-deficient rats were repleted with retinoic acid (RA; 4.2 micrograms/g diet); this treatment also effectively restored these vitamin-A-dependent processes. Therefore, despite the plasma-retinol-lowering property of 4-HPR, treatment with this retinoid did not impair NK cell number or function. Indeed, 4-HPR showed vitamin A activity similar to RA, and may stimulate NK cell cytotoxicity.</p>","PeriodicalId":77279,"journal":{"name":"Natural immunity","volume":"13 5","pages":"280-8"},"PeriodicalIF":0.0,"publicationDate":"1994-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18831808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antiviral activity of NK 1.1+ natural killer cells in C57BL/6 scid mice infected with murine cytomegalovirus.","authors":"R M Welsh, C L O'Donnell, L D Shultz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The activation, proliferation, and antiviral effects of natural killer (NK) cells were examined in a newly developed stock of mice, C57BL/6JSz mice homozygous for the severe combined immunodeficiency (scid) mutation. These mice lack functional T and B cells and express the NK 1.1 alloantigen. Such NK 1.1 expression facilitates the analysis of NK cells and their depletion in vivo with a monoclonal anti-NK 1.1 antibody. These mice, therefore, provide an excellent model to examine unambiguously the interactions between viral infections and NK cells in a system devoid of adaptive immune response mechanisms. Here we show that murine cytomegalovirus (MCMV) and lymphocytic choriomeningitis virus (LCMV) infections resulted in profound levels of NK cell activation. NK cells also proliferated greatly in response to LCMV but generally to a lesser degree in response to MCMV. Depletion of the NK cell activity in vivo caused substantial increases in MCMV synthesis and MCMV-induced pathology. These results further support the concept that NK cells are major regulators of MCMV pathogenesis.</p>","PeriodicalId":77279,"journal":{"name":"Natural immunity","volume":"13 5","pages":"239-45"},"PeriodicalIF":0.0,"publicationDate":"1994-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18831947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Changes in tumor-associated NK 1.1+ large granular lymphocyte precursors after cyclophosphamide injection: in vitro characterization and potential therapeutic application.","authors":"D M Krupke, J Fuller, C Aslakson, R Evans","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Large granular lymphocytes (LGLs) could be generated in vitro from tumor-associated cells (TACs) derived from the rhabdomyosarcoma, 76-9, but only after treatment of the tumor bearers with cyclophosphamide (CY). The ability to generate LGLs in vitro was dependent on the presence of high concentrations of recombinant interleukin (rIL)-2 and related to the phase of tumor regression induced by CY. Maximum yields of LGLs were obtained when TACs were derived on days 7 or 8 after CY injection. TACs derived on day 8 and grown in rIL-2 for 5 days were shown to express NK 1.1, B220, IL-2 receptor (IL-2R), Thy-1.2 and a late NK cell differentiation antigen identified by monoclonal antibody, 4H12. They did not express MAC-1, CD3, alpha/beta T cell receptor, CD4 or an early NK cell differentiation antigen identified by monoclonal antibody, 3C2. The expression of NK 1.1, B220, IL-2R, Thy-1.2 and 4H12 by TACs growing in rIL-2 was relatively stable over a 12-day period. IL-2-activated TACs were shown to lyse YAC-1 cells, the wild-type 76-9 tumor cells and two clones of the 76-9 tumor, as well as cells from an independently derived sarcoma, 77-23. Intratumor injection of IL-2-activated TACs or rIL-2 after CY injection induced a significant delay in the recurrence of tumor growth. The data suggest that the increase of IL-2-reactive cells after CY injection and their intratumor disposition may indicate a potential for in situ antitumor effects.</p>","PeriodicalId":77279,"journal":{"name":"Natural immunity","volume":"13 5","pages":"246-57"},"PeriodicalIF":0.0,"publicationDate":"1994-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18831804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F Bühling, D Kunz, D Reinhold, A J Ulmer, M Ernst, H D Flad, S Ansorge
{"title":"Expression and functional role of dipeptidyl peptidase IV (CD26) on human natural killer cells.","authors":"F Bühling, D Kunz, D Reinhold, A J Ulmer, M Ernst, H D Flad, S Ansorge","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The expression and functional role of dipeptidyl peptidase IV (DP IV, CD26, EC 3.4.14.5) was studied on human natural killer (NK) cells. Here we show that freshly isolated NK cells do express only low amounts of DP IV. However, after IL-2 stimulation of NK cells (70% purity) surface DP IV expression was significantly increased in a subpopulation (30%) of these cells. Specific DP IV inhibitors (Lys-[Z-(NO2)]-piperidide, Lys-[Z(NO2)]-thiazolidide) and polyclonal antibodies directed against the ectopeptidase suppressed DNA synthesis and cell cycle progression of NK cells. The natural cytotoxic activity of DP IV+ CD56+ cells was found unchanged in comparison to those of DP IV- CD56+ cells. DP IV inhibitors had no effect on the natural cytotoxicity of mononuclear cells. From these data we conclude that DP IV is involved in the regulation of proliferation of NK cells, whereas natural cytotoxicity seems to be regulated independently.</p>","PeriodicalId":77279,"journal":{"name":"Natural immunity","volume":"13 5","pages":"270-9"},"PeriodicalIF":0.0,"publicationDate":"1994-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18831807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Natural killer cell suppression of IgM production.","authors":"S Che, D P Huston","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The mechanisms by which natural killer (NK) cells regulate B cell function are not well understood. In this paper, the suppressive effects of NK cells on IgM production by lipopolysaccharide (LPS)-stimulated B cells were studied. We found that interleukin (IL)-2-activated NK (NKa) cells, but not unstimulated NK cells, suppressed IgM production by B cells stimulated with LPS. Suppression of antibody production required direct NKa-B cell contact, as demonstrated in cultures utilizing semiporous membranes for cell separation, and was the consequence of a reduction in the number of IgM-producing cells, as determined by enzyme-linked immunospot assays. Suppression could not be accounted for by cytotoxic mechanisms since the NKa cells caused neither cytolysis of 51Cr-labelled B cells or B cell apoptosis. While NKa-B cell contact was necessary for suppression, cell contact alone was not sufficient. Rather, both NKa-B cell contact and NKa production of interferon (IFN)-gamma were necessary. Since only IL-2-activated, but not unstimulated, NK cells suppressed IgM production, we investigated the potential for IL-4, which has been reported to downregulate IL-2-induced NK cell proliferation, to prevent NKa cell suppressive activity. While IL-4 antagonized IL-2-induced NK cell proliferation, it was completely ineffective in antagonizing NKa cell suppression of IgM production. The requirement for IL-2 activation of NK cells for suppression of IgM production suggests that NK cells may be part of a physiologic negative feedback mechanism to downregulate antibody production.</p>","PeriodicalId":77279,"journal":{"name":"Natural immunity","volume":"13 5","pages":"258-69"},"PeriodicalIF":0.0,"publicationDate":"1994-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18834060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}