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1.
The novel inhibitory NKR-P1C receptor and Ly49s3 identify two complementary, functionally distinct NK cell subsets in rats 总被引:3,自引:0,他引:3
Kveberg L Bäck CJ Dai KZ Inngjerdingen M Rolstad B Ryan JC Vaage JT Naper C 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(7):4133-4140
The proximal region of the NK gene complex encodes the NKR-P1 family of killer cell lectin-like receptors which in mice bind members of the genetically linked C-type lectin-related family, while the distal region encodes Ly49 receptors for polymorphic MHC class I molecules. Although certain members of the NKR-P1 family are expressed by all NK cells, we have identified a novel inhibitory rat NKR-P1 molecule termed NKR-P1C that is selectively expressed by a Ly49-negative NK subset with unique functional characteristics. NKR-P1C(+) NK cells efficiently lyse certain tumor target cells, secrete cytokines upon stimulation, and functionally recognize a nonpolymorphic ligand on Con A-activated lymphoblasts. However, they specifically fail to kill MHC-mismatched lymphoblast target cells. The NKR-P1C(+) NK cell subset also appears earlier during development and shows a tissue distribution distinct from its complementary Ly49s3(+) subset, which expresses a wide range of Ly49 receptors. These data suggest the existence of two major, functionally distinct populations of rat NK cells possessing very different killer cell lectin-like receptor repertoires. 相似文献
2.
Strain-dependent expression of four structurally related rat Ly49 receptors; correlation with NK gene complex haplotype and NK alloreactivity 总被引:5,自引:0,他引:5
Natural killer (NK) cells from certain rat strains promptly kill MHC allogeneic lymphocytes in vivo, a rejection phenomenon termed allogeneic lymphocyte cytotoxicity (ALC). ALC can be reproduced in vitro, and is preferentially mediated by a subset of NK cells expressing the Ly49 stimulatory receptor 3 (Ly49s3) in PVG strain
rats. Functional studies have suggested that Ly49s3 triggers NK cell alloreactivity, but its importance relative to other
Ly49 receptors has not been investigated. In this study, we have characterized three rat Ly49 receptors with close sequence
similarity to Ly49s3 in the extracellular region, i.e., Ly49s4, Ly49 inhibitory receptor 3 (Ly49i3), and Ly49i4. Similar to
Ly49s3, Ly49s4 mediated cellular activation while Ly49i4 inhibited NK cytolytic function. Ly49s4, -i3, and -i4 all reacted
with a previously described anti-Ly49s3 monoclonal antibody (mAb) (DAR13), but not a novel mAb (STOK6), which was shown to
be specific for Ly49s3. Expression of these Ly49 receptors varied markedly between inbred strains, in patterns related to
their NK gene complex (NKC) haplotype, and ability to mediate ALC. Three major groups of NKC haplotypes could be discerned
by restriction fragment length polymorphism analysis. Ly49s3 was present in strains from one of the groups, which corresponded
with the “high” ALC responders. Ly49s3 surface expression was also markedly reduced in the presence of its putative MHC class
Ib ligand(s) in MHC congenic strains. These data support the notion that Ly49s3 functions as a triggering MHC receptor both
in vitro and in vivo. MHC ligands for the other three Ly49 receptors remain to be determined. 相似文献
3.
Korten S Volkmann L Saeftel M Fischer K Taniguchi M Fleischer B Hoerauf A 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(10):5199-5206
Natural killer cell-associated direct cytotoxicity and cytokine production are crucial mechanisms for early innate host resistance against viruses, bacteria, or protozoa. The engagement of inhibitory NK cell receptors can influence host responses to viruses. However, these receptors have not been investigated to date in parasitic infections, and little is known about the role of NK cells in the defense against helminths. Therefore, we have correlated the frequencies of cells expressing the pan-NK marker DX5 and subsets bearing inhibitory Ly-49 receptors with worm survival and cytokine production during infection with Litomosoides sigmodontis in BALB/c mice (H2(d)), the only fully permissive model of filariasis. A marked influx of DX5(+)/CD3(-) NK cells and DX5(+)/CD3(+) T cells into the pleural cavity, where the parasites were located, was observed. The frequency of pleural NK cells expressing the H2(d)-reactive inhibitory receptors Ly-49A, Ly-49C, or Ly-49G2 declined most strongly compared with spleen and blood. In the peripheral blood, longitudinal analysis revealed an early and stable reduction of Ly-49C(+) and Ly-49G2(+) NK cells, a subsequent significant increase of the entire NK cell and DX5(+)/CD3(+) T cell populations, and a reduction in the Ly-49A(+) subset. The in vivo depletion of NK cells strongly enhanced the worm load and influenced IL-4 and IL-5 plasma levels. These data demonstrate a new role for NK cells in the host defense against filariae and, for the first time, alterations of Ly-49 receptor-expressing NK cell subsets in a parasitic infection. 相似文献
4.
Moretta L Biassoni R Bottino C Cantoni C Pende D Mingari MC Moretta A 《Microbes and infection / Institut Pasteur》2002,4(15):1539-1544
The past decade has witnessed important progress in our understanding of how natural killer (NK) cells function. This is primarily consequent to the identification and functional characterization of MHC-specific inhibitory receptors that allow NK cells to discriminate between normal cells and potentially harmful cells that have lost or express insufficient amounts of MHC class I molecules. More recently, a number of activating receptors or coreceptors have been identified that are involved in the process of natural cytotoxicity but may also play a role in the direct recognition of pathogen-associated structures. Surprisingly, none of the triggering receptors identified in NK cells appears to be involved in the "NK-like activity" of a subset of CD8(+) cytolytic T lymphocytes. In this case, lysis of NK-susceptible tumor target cells is the result of the TCR alpha/beta-mediated recognition of HLA-E. The potent cytolytic activity of NK cells as well as their unique mode of functioning may be exploited in therapy. An important breakthrough is the recent report that "alloreactive" NK cells, generated in haploidentical bone marrow transplantation in patients with acute myeloid leukemias, may efficiently prevent leukemic relapses as well as graft rejection and graft-vs.-host disease. This may lead to a true revolution in bone marrow transplantation, based on the exploitation of appropriate HLA-Cl I mismatches that can put NK cells in action. 相似文献
5.
Ly-49s3 is a promiscuous activating rat NK cell receptor for nonclassical MHC class I-encoded target ligands 总被引:6,自引:0,他引:6
Naper C Hayashi S Kveberg L Niemi EC Lanier LL Vaage JT Ryan JC 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(1):22-30
Previous studies of the rapid rejection of MHC-disparate lymphocytes in rats, named allogeneic lymphocyte cytotoxicity, have indicated that rat NK cells express activating receptors for nonclassical MHC class I allodeterminants from the RT1-C/E/M region. Using an expression cloning system that identifies activating receptors associated with the transmembrane adapter molecule DAP12, we have cloned a novel rat Ly-49 receptor that we have termed Ly-49 stimulatory receptor 3 (Ly-49s3). A newly generated anti-Ly-49s3 Ab, mAb DAR13, identified subpopulations of resting and IL-2-activated NK cells, but not T or B lymphocytes. Depletion of Ly-49s3-expressing NK cells drastically reduced alloreactivity in vitro, indicating that this subpopulation is responsible for a major part of the observed NK alloreactivity. DAR13-mediated blockade of Ly-49s3 inhibited killing of MHC-congenic target cells from the av1, n, lv1, and c haplotypes, but not from the u or b haplotypes. A putative ligand was mapped to the nonclassical MHC class I region (RT1-C/E/M) using intra-MHC recombinant strains. Relative numbers of Ly-49s3(+) NK cells were reduced, and surface levels of Ly-49s3 were lower, in MHC congenic strains expressing the putative Ly-49s3 ligand(s). In conclusion, we have identified a novel Ly-49 receptor that triggers rat NK cell-mediated responses. 相似文献
6.
Cutting edge: the mouse NK cell-associated antigen recognized by DX5 monoclonal antibody is CD49b (alpha 2 integrin, very late antigen-2) 总被引:8,自引:0,他引:8
Arase H Saito T Phillips JH Lanier LL 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(3):1141-1144
DX5 mAb is a useful reagent because it stains NK cells from all mouse strains examined. We have identified the molecule recognized by DX5 mAb by using a retrovirus-mediated expression cloning system. A 5-kb cDNA encoding a protein that is reactive with the DX5 mAb was isolated from a NK cell cDNA library, and this molecule was identical with CD49b (very late Ag-2, alpha(2) integrin). The DX5 mAb reacted with transfectants expressing CD49b, and binding of DX5 to the NK cells and CD49b transfectants was blocked in the presence of other anti-CD49b mAbs. When NK1.1(+) NK cells were cultured with IL-2, they progressively lost reactivity with DX5 mAb as a consequence of cellular proliferation. Cytotoxicity mediated by the DX5(+) NK cells was dramatically higher as compared with DX5(-) NK cells. Therefore, DX5 mAb recognizes CD49b and can be used to define functionally distinct subsets of NK cells. 相似文献
7.
Shauna M. Collins Courtney E. Bakan Gina D. Swartzel Craig C. Hofmeister Yvonne A. Efebera Hakju Kwon Gary C. Starling David Ciarlariello Shakthi Bhaskar Edward L. Briercheck Tiffany Hughes Jianhua Yu Audie Rice Don M. Benson Jr. 《Cancer immunology, immunotherapy : CII》2013,62(12):1841-1849
Elotuzumab is a monoclonal antibody in development for multiple myeloma (MM) that targets CS1, a cell surface glycoprotein expressed on MM cells. In preclinical models, elotuzumab exerts anti-MM efficacy via natural killer (NK)-cell-mediated antibody-dependent cellular cytotoxicity (ADCC). CS1 is also expressed at lower levels on NK cells where it acts as an activating receptor. We hypothesized that elotuzumab may have additional mechanisms of action via ligation of CS1 on NK cells that complement ADCC activity. Herein, we show that elotuzumab appears to induce activation of NK cells by binding to NK cell CS1 which promotes cytotoxicity against CS1(+) MM cells but not against autologous CS1(+) NK cells. Elotuzumab may also promote CS1–CS1 interactions between NK cells and CS1(+) target cells to enhance cytotoxicity in a manner independent of ADCC. NK cell activation appears dependent on differential expression of the signaling intermediary EAT-2 which is present in NK cells but absent in primary, human MM cells. Taken together, these data suggest elotuzumab may enhance NK cell function directly and confer anti-MM efficacy by means beyond ADCC alone. 相似文献
8.
Mouse CD94 participates in Qa-1-mediated self recognition by NK cells and delivers inhibitory signals independent of Ly-49 总被引:1,自引:0,他引:1
Toyama-Sorimachi N Taguchi Y Yagita H Kitamura F Kawasaki A Koyasu S Karasuyama H 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(6):3771-3779
Inhibitory receptors expressed on NK cells recognize MHC class I molecules and transduce negative signals to prevent the lysis of healthy autologous cells. The lectin-like CD94/NKG2 heterodimer has been studied extensively as a human inhibitory receptor. In contrast, in mice, another lectin-like receptor, Ly-49, was the only known inhibitory receptor until the recent discovery of CD94/NKG2 homologues in mice. Here we describe the expression and function of mouse CD94 analyzed by a newly established mAb. CD94 was detected on essentially all NK and NK T cells as well as small fractions of T cells in all mouse strains tested. Two distinct populations were identified among NK and NK T cells, CD94(bright) and CD94(dull) cells, independent of Ly-49 expression. The anti-CD94 mAb completely abrogated the inhibition of target killing mediated by NK recognition of Qa-1/Qdm peptide on target cells. Importantly, CD94(bright) but not CD94(dull) cells were found to be functional in the Qa-1/Qdm-mediated inhibition. In the presence of the mAb, activated NK cells showed substantial cytotoxicity against autologous target cells as well as enhanced cytotoxicity against allogeneic and "missing self" target cells. These results suggest that mouse CD94 participates in the protection of self cells from NK cytotoxicity through the Qa-1 recognition, independent of inhibitory receptors for classical MHC class I such as Ly-49. 相似文献
9.
In haplo-identical hematopoietic transplantation, donor vs. recipient natural killer (NK) cell alloreactivity derives from a mismatch between donor NK clones bearing inhibitory killer cell Ig-like receptors (KIR) for self-HLA class I molecules and their HLA class I ligands (KIR ligands) on recipient cells. When faced with mismatched allogeneic targets, these NK clones sense the missing expression of self-HLA class I alleles and mediate alloreactions. KIR ligand mismatches in the GvH direction trigger donor vs. recipient NK cell alloreactions, which improve engraftment, do not cause GvHD and control relapse in AML patients . The mechanism whereby alloreactive NK cells exert their benefits in transplantation has been elucidated in mouse models. The infusion of alloreactive NK cells ablates (i) leukemic cells, (ii) recipient T cells that reject the graft and (iii) recipient DC that trigger GvHD, thus protecting from GvHD. 相似文献
10.
Wang LL Chu DT Dokun AO Yokoyama WM 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(10):5215-5220
Murine NK cells express inhibitory receptors belonging to the C-type lectin-like (Ly-49, CD94/NKG2) and Ig superfamily-related (gp49) receptors. The murine gp49B receptor displays structural homology with human killer inhibitory receptors, and was previously identified to be a receptor on mast cells and activated NK cells. The gp49B receptor is highly related to gp49A, a receptor with unknown function. In this study, using a novel mAb produced against soluble gp49B molecules that cross-reacts with gp49A, we examined the cellular distribution and function of these receptors. gp49 is constitutively expressed on cells of the myeloid lineage throughout development, as well as on mature cells. Importantly, gp49 is not expressed on spleen- and liver-derived lymphocytes, including NK cells, but its expression is induced in vitro on NK cells following IL-2 stimulation, or in vivo by infection with murine CMV. Molecular studies revealed that both the immunoreceptor tyrosine-based inhibitory motif-containing gp49B as well as immunoreceptor tyrosine-based inhibitory motif-less gp49A receptors are up-regulated on NK cells following murine CMV infection. When co-cross-linked with NK1.1, gp49B can inhibit NK1.1-mediated cytokine release by NK cells. Taken together, these studies demonstrate that the expression of gp49B on NK cells is regulated, providing the first example of an in vivo activation-induced NK cell inhibitory receptor, in contrast to the constitutively expressed Ly49 family. 相似文献
11.
Warren HS 《Immunology and cell biology》1999,77(6):544-551
Human NK cells labelled intracellularly with the fluorescent dye 5- and 6-carboxyfluorescein diacetate succinimidyl ester (CFSE) were used to assess the effect of ligating class I MHC receptors on NK cell division. The NK cell lines used in these studies expressed a selection of the killer immunoglobulin-like receptors CD158b and CD158a and the CD94/NKG2 family of C-type lectin receptors. The NK cells were cultured in medium containing recombinant (r)IL-2 and receptors were ligated using plastic bound mAb or using soluble murine IgG mAb and FcRII+ gamma-irradiated murine P815 cells. The results obtained show that ligating class I MHC-activating receptors in either culture system stimulates NK cells to divide. Quantitative analysis of cell division reveals that a substantial loss of NK progenitor cells occurs when NK cell-activating receptors are ligated using plastic bound mAb, consistent with concomitant activation-induced cell death. By contrast, progenitor cell loss is prevented when activating receptors are ligated using soluble mAb and P815 cells, suggesting a role for cellular costimulation in cell survival. When inhibitory receptors are coligated with activating receptors using soluble mAb and P815 cells, NK cell division is inhibited. These results demonstrate the potential importance of the activating and inhibitory class I MHC receptors in regulating NK cell proliferation. 相似文献
12.
Naper C Dai KZ Kveberg L Rolstad B Niemi EC Vaage JT Ryan JC 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(5):2702-2711
The Ly49 family of lectin-like receptors in rodents includes both stimulatory and inhibitory members. Although NK alloreactivity in mice is regulated primarily by inhibitory Ly49 receptors, in rats activating Ly49 receptors are equally important. Previous studies have suggested that activating rat Ly49 receptors are triggered by polymorphic ligands encoded within the nonclassical class Ib region of the rat MHC, RT1-CE/N/M, while inhibitory Ly49 receptors bind to widely expressed classical class Ia molecules encoded from the RT1-A region. To further investigate rat Ly49-mediated regulation of NK alloreactivity, we report in this study the identification and characterization of two novel paired Ly49 receptors that we have termed Ly49 inhibitory receptor 5 (Ly49i5) and Ly49 stimulatory receptor 5 (Ly49s5). Using a new mAb (mAb Fly5), we showed that Ly49i5 is an inhibitory receptor that recognizes ligands encoded within the class Ib region of the u and l haplotypes, while the structurally related Ly49s5 is an activating receptor that recognizes class Ib ligands of the u haplotype. Ly49s5 is functionally expressed in the high NK-alloresponder PVG strain, but not in the low alloresponder BN strain, in which it is a pseudogene. Ly49s5 is hence not responsible for the striking anti-u NK alloresponse previously described in BN rats (haplotype n), which results from repeated alloimmunizations with u haplotype cells. The present studies support the notion of a complex regulation of rat NK alloreactivity by activating and inhibitory Ly49 members, which may be highly homologous in the extracellular region and bind similar class Ib-encoded target ligands. 相似文献
13.
Robbins SH Terrizzi SC Sydora BC Mikayama T Brossay L 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(12):5876-5885
The killer cell lectin-like receptor G1 (KLRG1) is the mouse homologue of the rat mast cell function-associated Ag and contains a tyrosine-based inhibitory motif in its cytoplasmic domain. It has been demonstrated that KLRG1 is induced on activated NK cells and that KLRG1 can inhibit NK cell effector functions. In this study, we show that in naive C57BL/6 mice KLRG1 is expressed on a subset of CD44(high)CD62L(low) T cells. KLRG1 expression can be detected on a small number of V(alpha)14i NK T cells but not on CD8alphaalpha(+) intraepithelial T cells that are either TCRgammadelta(+) or TCRalphabeta(+). We also show that KLRG1 expression is dramatically induced on approximately 50% of the CD8(+) T cells during both a viral and a parasitic infection. Interestingly, during Toxoplasma gondii infection, KLRG1 is up-regulated on CD4(+) T cells. Although KLRG1 expression can be induced on both NK cells and T cells, the molecular mechanism leading to the induction of KLRG1 differs in these two subsets of cells. Indeed, the up-regulation of KLRG1 on NK cells can be driven in vivo by cytokines, whereas KLRG1 cannot be induced on CD8(+) T cells by cytokines. In addition, although induction of KLRG1 on T cells appears to require TCR engagement in vivo, TCR engagement is not sufficient for KLRG1 induction in vitro. Taken together, these data suggest that the expression and induction of KLRG1 on T cells are tightly regulated. This could have important biological consequences on T cell activation and homeostasis. 相似文献
14.
Ly49D is a natural killer (NK) cell activation receptor that is responsible for differential mouse inbred strain-determined lysis of Chinese hamster ovary (CHO) cells. Whereas C57BL/6 NK cells kill CHO, BALB/c-derived NK cells cannot kill because they lack expression of Ly49D. Furthermore, the expression of Ly49D, as detected by monoclonal antibody 4E4, correlates well with CHO lysis by NK cells from different inbred strains. However, one discordant mouse strain was identified; C57L NK cells express the mAb 4E4 epitope but fail to lyse CHO cells. Herein we describe a Ly49 molecule isolated from C57L mice that is recognized by mAb 4E4 (anti-Ly49D). Interestingly, this molecule shares extensive similarity to Ly49D(B6) in its extracellular domain, but its cytoplasmic and transmembrane domains are identical to the inhibitory receptor Ly49A(B6), including a cytoplasmic ITIM. This molecule bears substantial overall homology to the previously cloned Ly49O molecule from 129 mice the serologic reactivity and function of which were undefined. Cytotoxicity experiments revealed that 4E4(+) LAK cells from C57L mice failed to lyse CHO cells and inhibited NK cell function in redirected inhibition assays. MHC class I tetramer staining revealed that the Ly49O(C57L)-bound H-2D(d) and lysis by 4E4(+) C57L LAK cells is inhibited by target H-2D(d). The structural basis for ligand binding was also examined in the context of the recent crystallization of a Ly49A-H-2D(d) complex. Therefore, this apparently "chimeric" Ly49 molecule serologically resembles an NK cell activation receptor but functions as an inhibitory receptor. 相似文献
15.
Natural killer (NK) cell function, based on the expression of activating and inhibitory natural killer receptors (NKRs), may become abnormal during human immunodeficiency virus (HIV) infection. In this study, we investigated changes in receptor expression with individual and combinational analysis on NK cell subsets in HIV-infected Chinese. The results showed that natural killer group 2 member D (NKG2D) expression on total NK cells decreased significantly in HIV infection, while the expressions of natural killer group 2 member A (NKG2A) and killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail 1 (KIR3DL1) on total NK cells were not significantly different between any of the groups including HIV-positive treatment-naïve group, AIDS treatment-naïve group, HAART-treatment AIDS group and HIV-negative control group. Individual analysis of NKG2A+ and KIR3DL1+ cells revealed no significant differences in expression in any NK cell subsets between any of the groups, but the combinational analysis of NKG2D−NKG2A+, and NKG2D−KIR3DL1+ on the NK CD56dim cell subset in the AIDS group were increased compared to the HIV-negative control group. On the contrary, NKG2D−NKG2A+ expression on the CD56bright subset decreased in the AIDS group compared to the control group. Highly active antiretroviral therapy (HAART) treatment almost completely restored the levels of these receptor expressions. The results indicate that the distinct alteration of activating and inhibitory NKR expression on NK cells and its subsets occurred during HIV progression. Moreover, the imbalanced change of activating and inhibitory NKRs on NK cells and its subsets may explain the impaired NK cell immunity in HIV infected individuals. 相似文献
16.
A novel alloantigen-specific CD8+PD1+ regulatory T cell induced by ICOS-B7h blockade in vivo 总被引:1,自引:0,他引:1
Izawa A Yamaura K Albin MJ Jurewicz M Tanaka K Clarkson MR Ueno T Habicht A Freeman GJ Yagita H Abdi R Pearson T Greiner DL Sayegh MH Najafian N 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(2):786-796
Delayed ICOS-B7h signal blockade promotes significant prolongation of cardiac allograft survival in wild-type but not in CD8-deficient C57BL/6 recipients of fully MHC-mismatched BALB/c heart allografts, suggesting the possible generation of CD8(+) regulatory T cells in vivo. We now show that the administration of a blocking anti-ICOS mAb results in the generation of regulatory CD8(+) T cells. These cells can transfer protection and prolong the survival of donor-specific BALB/c, but not third party C3H, heart grafts in CD8-deficient C57BL/6 recipients. This is unique to ICOS-B7h blockade, because B7 blockade by CTLA4-Ig prolongs graft survival in CD8-deficient mice and does not result in the generation of regulatory CD8(+) T cells. Those cells localize to the graft, produce both IFN-gamma and IL-4 after allostimulation in vitro, prohibit the expansion of alloreactive CD4(+) T cells, and appear to mediate a Th2 switch of recipient CD4(+) T cells after adoptive transfer in vivo. Finally, these cells are not confined to the CD28-negative population but express programmed death 1, a molecule required for their regulatory function in vivo. CD8(+)PD1(+) T cells suppress alloreactive CD4(+) T cells but do not inhibit the functions by alloreactive CD8(+) T cells in vitro. These results describe a novel allospecific regulatory CD8(+)PD1(+) T cell induced by ICOS-B7h blockade in vivo. 相似文献
17.
Dominique Pinard N.-O. Olsson William H. Chambers François Martin 《Cancer immunology, immunotherapy : CII》1996,42(1):15-23
NKR-P1 has been identified as a triggering structure selectively expressed on rat natural killer (NK) cells and adherent
lymphokine-activated killer (A-LAK) cells. In vivo treatment with anti-NKR-P1 monoclonal antibody (mAb 3.2.3) was shown to
induce complete inhibition of NK cytotoxicity and elimination of LAK cell precursors in Lewis and Fisher rat strains. We investigated
the effects of mAb 3.2.3 in a colon tumor model in BDIX rats. Inoculation of animals with mAb 3.2.3 even at very high doses
induced a strong but incomplete inhibition of NK cytotoxicity in nylon-wool-non-adherent spleen and peripheral blood cells.
Generation of adherent A-LAK cells from their spleen precursors was also strongly but not fully inhibited. We also investigated
the effect of treatment with mAb 3.2.3 on the tumorigenicity of the NK-sensitive REGb cell line. When subcutaneously inoculated
in syngeneic animals, REGb cells induce tumors that first grow for 2 weeks, then spontaneously regress and disappear. In contrast
with previous results using anti-asialoGM1, no significant difference in tumor growth was observed between rats treated with
mAb 3.2.3 and control animals, even with a long-term treatment. In vitro, mAb 3.2.3 exhibited the same incomplete efficiency.
Nylon-wool-non-adherent spleen cells treated with mAb 3.2.3 plus complement were completely free of 3.2.3bright cells, but retained a substantial NK activity and generated LAK cells after culture with IL-2. After an overnight incubation
in standard medium of 3.2.3-depleted spleen cells, 3.2.3bright cells were partially recovered and the NK cytotoxic activity, as well as the generation of LAK cells, was significantly enhanced.
These results suggest that a strong expression of NKR-P1 is not required for BDIX mononuclear cells to exhibit NK function
and generate LAK cells under IL-2 activation.
Received: 11 July 1995 / Accepted: 16 November 1995 相似文献
18.
Characterization of developmental pathway of natural killer cells from embryonic stem cells in vitro
In vitro differentiation of embryonic stem (ES) cells is often used to study hematopoiesis. However, the differentiation pathway of lymphocytes, in particular natural killer (NK) cells, from ES cells is still unclear. Here, we used a multi-step in vitro ES cell differentiation system to study lymphocyte development from ES cells, and to characterize NK developmental intermediates. We generated embryoid bodies (EBs) from ES cells, isolated CD34(+) EB cells and cultured them on OP9 stroma with a cocktail of cytokines to generate cells we termed ES-derived hematopoietic progenitors (ES-HPs). EB cell subsets, as well as ES-HPs derived from EBs, were tested for NK, T, B and myeloid lineage potentials using lineage specific cultures. ES-HPs derived from CD34(+) EBs differentiated into NK cells when cultured on OP9 stroma with IL-2 and IL-15, and into T cells on Delta-like 1-transduced OP9 (OP9-DL1) with IL-7 and Flt3-L. Among CD34(+) EB cells, NK and T cell potentials were detected in a CD45(-) subset, whereas CD45(+) EB cells had myeloid but not lymphoid potentials. Limiting dilution analysis of ES-HPs generated from CD34(+)CD45(-) EB cells showed that CD45(+)Mac-1(-)Ter119(-) ES-HPs are highly enriched for NK progenitors, but they also have T, B and myeloid potentials. We concluded that CD45(-)CD34(+) EB cells have lymphoid potential, and they differentiate into more mature CD45(+)Lin(-) hematopoietic progenitors that have lymphoid and myeloid potential. NK progenitors among ES-HPs are CD122(-) and they rapidly acquire CD122 as they differentiate along the NK lineage. 相似文献
19.
A phenyl-beta-galactoside-specific monoclonal antibody reactive with murine and rat NK cells 总被引:1,自引:0,他引:1
V E Miller A E Lagarde B M Longenecker A H Greenberg 《Journal of immunology (Baltimore, Md. : 1950)》1986,136(8):2968-2974
The phenyl-beta-galactoside (phi-beta-gal)-specific monoclonal antibody (mAb) 49H.8 cross-reacts with the terminal disaccharide structure of the asialo GM1 (AGM1) molecule. It was found to react with phi-beta-gal determinants on murine and rat splenic natural killer (NK) cells, as measured by complement depletion studies. Flow cytometric analysis identified the antigen on two IL 2-dependent cloned murine NK cell lines and the rat large granular lymphocyte leukemia RNK. We have compared the 49H.8 reactivity to that of anti-AGM1 antisera (alpha-AGM1) on NK cells and a panel of NK related killer cells, including bone marrow-derived killer cells, lymphokine-activated killer cells (LAK), and anomalous killer cells (AK). We found that the 49H.8 specificity closely paralleled that of alpha-AGM1. When tested against Con A-reactive T cells, the 49H.8 mAb was less reactive than the alpha-AGM1, indicating that it may be a more specific marker for splenic NK populations than the alpha-AGM1. 相似文献
20.
Solana R Casado JG Delgado E DelaRosa O Marín J Durán E Pawelec G Tarazona R 《Cancer immunology, immunotherapy : CII》2007,56(1):101-109
In recent years, studies on the molecular and cellular mechanisms of immune responses against melanoma have contributed to a better understanding of how these tumours can be recognised by cytotoxic cells and the mechanisms they have developed to escape from innate and adaptive immunity. Lysis of melanoma cells by natural killer (NK) cells and cytolytic T cells is the result of a fine balance between signals transmitted by activating and inhibitory receptors. In addition to the T cell receptor, these were initially described as NK cell-associated receptors (NKRs) and were later also found on subsets of T lymphocytes, particularly effector-memory and terminally differentiated CD8 T cells. An increase of NKR(+)CD8(+) T cells has been found in melanoma patients, correlating with the expansion of differentiated effector CD8(+)CD28(null) CD27(null) T cells. NKRs can regulate the lysis of target cells expressing appropriate ligands. Activating receptors recognise ligands on tumours whereas inhibitory receptors are specific for MHC class I antigens and sense missing self. Altered expression of MHC class I antigens is frequently found on melanoma cells, preventing recognition by specific cytolytic T cells but favouring NK cell recognition. Changes in the expression of NKR-ligands in melanoma contribute in explaining the differences in the capacity of cytotoxic immune cells to control melanoma growth and dissemination. 相似文献