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1.
De Maria A Fogli M Costa P Murdaca G Puppo F Mavilio D Moretta A Moretta L 《European journal of immunology》2003,33(9):2410-2418
Signals leading to NK cell triggering are primarily mediated by natural cytotoxicity receptors (NCR) upon binding to as-yet-undefined cell surface ligand(s) on normal hematopoietic cells, pathogen-infected cells or tumor cells. In this study we tried to determine whether the decreased NK cell cytolytic function that is observed in HIV-1-infected patients may be related to a decreased expression of NCR. In HIV-1-infected patients, freshly drawn, purified NK cells expressed significantly decreased surface densities of NKp46 and NKp30 NCR. The low surface density of NKp46, NKp30 and NKp44 was also confirmed in in-vitro-activated NK cell populations and NK cell clones derived from HIV-1 patients compared with uninfected donors. This defective NCR expression in HIV-1 patients was associated with a parallel decrease of NCR-mediated killing of different tumor target cells. Thus, the present study indicates that the defective expression of NCR represents at least one of the possible mechanisms leading to the impaired NK cell function in HIV-1 infection and it can contribute to explain the relatively high frequency of opportunistic tumors reported in cohorts of untreated patients before the occurrence of profound immunosuppression (<200 CD4(+) cells/mm(3)). 相似文献
2.
Roberto Biassoni Gerrit Koopman Elisabetta Ugolotti Manuela Fogli Rob Dubbes Paola Costa Maria C. Mingari Edward J. D. Greenwood Lorenzo Moretta Andrea DeMaria Jonathan L. Heeney 《European journal of immunology》2010,40(5):1440-1450
HIV‐1 infection in humans results in an early and progressive NK cell dysfunction and an accumulation of an “anergic” CD56? CD16+ NK subset, which is characterised by low natural cytotoxicity receptor expression and low cytokine producing capacity. In contrast to humans, chimpanzee NK cells do not display a distinguishable CD56bright and CD56dim subset but, as shown here, could be subdivided into functionally different CD8+ and CD8? subsets. The CD8+ NK cells expressed significantly higher levels of triggering receptors including NKp46 and, upon in vitro activation, produced more IFN‐γ, TNF‐α and CD107 than their CD8? counterparts. In addition, chimpanzee CD8? NK cells had relatively high levels of HLA‐DR expression, suggestive of an activated state. Killing inhibitory receptors were expressed only at low levels; however, upon in vitro stimulation, they were up‐regulated in CD8+ but not in CD8? NK cells and were functionally capable of inhibiting NKp30‐triggered killing. In contrast to HIV‐1‐infected humans, infected chimpanzees maintained their dominant CD8+ NK cell population, with high expression of natural cytotoxicity receptors. 相似文献
3.
Approximately 20% of normal blood lymphocytes expressing the T-helper (Leu 3/T 4+) surface phenotype display natural killer (NK)-like features such as cytoplasmic granules and the ability to bind NK-cell targets. In this study, we have assessed the frequency, phenotypic features, and functional capabilities of such cells in a variety of lymphoid malignancies or solid tumors. In each patient group, the percentage of granular lymphocytes within the Leu 3/T 4+ T-helper subset was significantly increased. A large percentage of these cells coexpressed the Leu 7 or Leu 15 marker. When Leu 3+ cells from patients with high proportions of such NK-like cells (or Leu 3+-Leu 15+ cells from selected patients) were isolated with a fluorescence-activated cell sorter, these cells did not proliferate in response to allogeneic cells or T-cell mitogens, nor did they provide help for B-cell differentiation. They also did not suppress T-cell proliferative responses or B-cell differentiation. Freshly prepared Leu 3+ granular lymphocytes did not display NK-cell cytotoxic functions. However, after short-term culture in the presence of phytohemagglutinin (PHA), Leu 3+-Leu 15+ cells expressed T-cell growth factor (TCGF) receptors, had a detectable proliferative response to exogenous TCGF, and acquired the ability to lyse NK-cell targets. These studies demonstrate that, in a variety of malignancies, the lymphocyte subpopulation expressing the T-helper (Leu 3/T 4+) phenotype may be comprised largely of cells with NK-like features and functional capabilities distinct from those of classical helper T cells. 相似文献
4.
Functional characterization of a conserved pair of NKR‐P1 receptors expressed by NK cells and T lymphocytes in liver and gut
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Lise Kveberg Amanda Sudworth Izabela Todros‐Dawda Marit Inngjerdingen John T. Vaage 《European journal of immunology》2015,45(2):501-512
Natural killer cell receptor protein 1 (NKR‐P1) molecules are C‐type lectin‐like receptors modulating cellular responses toward target cells expressing C‐type lectin‐like related (Clr) molecules. Although the function of the prototypic rat NKR‐P1A receptor and its inhibitory counterpart NKR‐P1B are known, little is known about NKR‐P1F and NKR‐P1G apart from their promiscuity for Clr ligands. Here we generated mAbs against both receptors for phenotypic and functional analyses in rat tissues. NKR‐P1F induced redirected lysis and robust Ca2+ signaling in NK cells, which were prevented by simultaneous engagement of NKR‐P1G. NKR‐P1G also inhibited NK‐cell lysis of Clr transfectants. NKR‐P1F was expressed by most NK cells and NKR‐P1A+ T cells in all tissues analyzed, and by many NKR‐P1A? intestinal T cells, while NKR‐P1G was expressed by subsets of these cells with highest prevalence in gut and liver. In the intraepithelial compartment, the proportion of NKR‐P1A+ and NKR‐P1F+ cells was high at birth and thereafter declined, while NKR‐P1B+ and NKR‐P1G+ cells increased with age. Expression levels were also modulated by cytokines, with an increase of NKR‐P1B and NKR‐P1G induced by inflammatory cytokines, and a reduction of NKR‐P1A by TGF‐β. The physiological impact of NKR‐P1 receptors might thus be dependent on age, tissue, and inflammatory status. 相似文献
5.
Jean E. Merrill 《Journal of clinical immunology》1983,3(1):42-50
Though purported to be identical cells (or in identical populations of cells), the natural killer (NK) cell mediating spontaneous natural cytotoxicity and the killer (K) cell mediating antibody-dependent cellular cytotoxicity (ADCC) may not be totally identical, at least in susceptibility to regulation by the immunomodulators prostaglandin E1 (PGE1) and interferon (IFN). We demonstrate here that NK cells are always enhanced by IFN, while K cells are inhibited from binding targets, resulting in fewer effectors at optimal concentrations of antibody. Only at 10- to 100-fold suboptimal concentrations of antibody is ADCC activity enhanced. As measured by magnitude of inhibition and dose-response titration, ADCC activity is less sensitive to the effects of PGE1 than is NK activity in the51Cr release assay and single-cell assay. After overnight incubation with or without PGE1, whatever sensitivity ADCC activity had to PGE1 is lost. However, NK cells incubated in the presence of PGE1 overnight are still sensitive to inhibition. Indomethacin boosts NK activity without having any effect on ADCC activity. Finally, NK activity is substantially reduced by overnight incubation of cells at room temperature, which has no effect on K cells. 相似文献
6.
Transforming growth factor (TGF)-beta1 exerts autocrine and paracrine effects on hematopoiesis. Here, we have attempted to evaluate the effect of endogenous TGF-beta1 on early erythroid development from primitive human hematopoietic stem cells (HSCs) and to assess the effects of TGF-beta1 on different phases of erythropoiesis. Cord blood CD34(+)CD38(-) lineage-marker-negative (Lin(-)) cells were cultured in serum-free conditions using various combinations of stem cell factor (SCF), erythropoietin (Epo), and TGF-beta-neutralizing antibody. Generation of erythroid progenitors was assessed using colony assay and flow cytometry. Terminal erythroid differentiation was examined when SCF/Epo-stimulated cells were recultured in the presence of Epo with and without TGF-beta1. Anti-TGF-beta augmented the proliferation of CD34(+)CD38(-)Lin(-) cells (day 21) in SCF-stimulated (6.4-fold +/- 1.5-fold) and SCF/Epo-stimulated (2.9-fold +/- 1.2-fold) cultures. Cells stimulated by SCF/Epo underwent similar levels of erythroid differentiation with and without anti-TGF-beta. While SCF alone stimulated the production of tryptase-positive mast cells, cells stimulated by SCF/anti-TGF-beta were predominantly erythroid (CD36(+)CD14(-) and glycophorin A positive). A distinct expansion of erythroid progenitors (CD34(+)CD36(+)CD14(-)) with the potential to form erythroid colonies was seen, revealing early Epo-independent erythroid development. In contrast, the kinetics of erythroid progenitor generation from primitive HSCs indicate that TGF-beta1 is not inhibitory in late erythropoiesis, but it accelerated the conversion of large BFU-E into colony-forming units-erythroid. Finally, TGF-beta1 accelerated Epo-induced terminal erythroid differentiation and resulted in a greater level of enucleation (22% +/- 6% versus 7% +/- 3%) in serum-free conditions. Serum addition stimulated enucleation (54% +/- 18%), which was lower (26% +/- 14%) with anti-TGF-beta, suggesting that optimal erythroid enucleation is Epo dependent, requiring serum factors including TGF-beta1. 相似文献
7.
CS1 (CRACC, novel Ly9) is a novel member of the CD2 family expressed on natural killer (NK), T and stimulated B cells. Although the cytoplasmic domain of CS1 contains immunoreceptor tyrosine-based switch motifs (ITSM), which enables to recruite signaling lymphocyte activation molecule (SLAM)-associated protein (SAP/SH2D1A), it activates NK cells in the absence of a functional SAP. CS1 is a self ligand and homophilic interaction of CS1 regulates NK cell cytolytic activity. Here we have identified a novel splice variant of CS1 (CS1-S), which lacks ITSM. Human NK cells express mRNA for both wild-type CS1 (CS1-L) and CS1-S and their expression level remained steady upon various stimulations. To determine the function of each isoform, cDNA for CS1-L and CS1-S were transfected into the rat NK cell line RNK-16 and functionally tested using redirected cytotoxicity assays and calcium flux experiments. CS1-L was able to mediate redirected cytotoxicity of P815 target cells in the presence of monoclonal antibody against CS1 and a rise in intracellular calcium within RNK-16 cells, suggesting that CS1-L is an activating receptor, whereas CS1-S showed no effects. Interestingly, SAP associated with unstimulated CS1-L and dissociated upon pervanadate stimulation. These results indicate that CS1-L and CS1-S may differentially regulate human NK cell functions. 相似文献
8.
We have reported earlier that pretreatment of mice with neem leaf preparation (NLP) causes prophylactic growth inhibition of murine Ehrlich's carcinoma (EC) and B16 melanoma. Using adoptive cell transfer technology, here we have established that NLP-mediated activation of immune cells may be involved in tumor growth restriction. Mononuclear cells from blood and spleen of NLP-activated Swiss and C57BL/6 mice causes enhanced cytotoxicity to murine EC cells in vitro. Fractionation of spleen cells exhibited greater percentage of tumor cell lysis in macrophage and B-cell-depleted NK and T-cell-rich fractions. Flow cytometric analysis revealed in both blood and spleen, NK cells (DX5+ or NK1.1+) and NK-T cells (CD3+/DX5+ or CD3+/NK1.1+) were increased in number in Swiss, C57BL/6 and athymic nude mice after pretreatment with NLP. NLP-stimulated spleen cells showed greater secretion of TNFalpha and IFNgamma. Thus, NLP-activated NK and NK-T cells in mice may regulate tumor cell cytotoxicity by enhancing the secretion of different cytotoxic cytokines. 相似文献
9.
Cristina Cerboni Angela Gismondi Gabriella Palmieri Mario Piccoli Luigi Frati Angela Santoni 《European journal of immunology》1998,28(3):1005-1015
Phosphatidylinositol 3-kinase (Pl-3K) plays a key role in several cellular processes, including mitogenesis, apoptosis, actin reorganization and vesicular trafficking. The molecular events involved in its activation have not been fully elucidated and several reports indicate that a key event for enzyme activation is the interaction of the SH2 domains of the p85 regulatory subunit of Pl-3K with tyrosine-phosphorylated proteins. In this study, we investigated the involvement of the product of the proto-oncogene c-Cbl in the activation of Pl-3K triggered by CD16 in human NK cells and the possible mechanisms leading to Pl-3K recruitment to the plasma membrane. Our results indicate that stimulation of NK cells through CD16 results in a rapid tyrosine phosphorylation of Cbl, which is constitutively associated with Grb2 and forms an activation-dependent complex with the p85 subunit of Pl-3K. In addition, we detected the presence of the Grb2-associated tyrosine-phosphorylated p36 and Shc proteins in anti-Cbl and anti-p85 immunoprecipitates from CD16-stimulated NK cell lysates. Upon CD16 stimulation, Pl-3K activity was found associated with Cbl and to a lesser extent with Grb2 and Shc as well as with the ζ chain of the CD16 receptor complex. Overall these results suggest that the formation of a complex containing either Shc or pp36 associated with Grb2, Cbl and the p85 subunit of Pl-3K is one of the major mechanisms which might couple CD16 to the Pl-3K pathway in NK cells. 相似文献
10.
Increased frequency and function of KIR2DL1–3+ NK cells in primary HIV‐1 infection are determined by HLA‐C group haplotypes
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Christian Körner Mitchell E. Granoff Molly A. Amero Michael N. Sirignano Sagar A. Vaidya Stephanie Jost Todd M. Allen Eric S. Rosenberg Marcus Altfeld 《European journal of immunology》2014,44(10):2938-2948
The acquisition and maintenance of NK‐cell function is mediated by inhibitory killer‐cell immunoglobulin‐like receptors (KIRs) through their interaction with HLA class I molecules. Recently, HLA‐C expression levels were shown to be correlated with protection against multiple outcomes of HIV‐1 infection; however, the underlying mechanisms are poorly understood. As HLA‐C is the natural ligand for the inhibitory receptors KIR2DL1 and KIR2DL2/3, we sought to determine whether HLA‐C group haplotypes affect NK‐cell responses during primary HIV‐1 infection. The phenotypes and functional capacity of NK cells derived from HIV‐1‐positive and HIV‐1‐negative individuals were assessed (N = 42 and N = 40, respectively). HIV‐1 infection was associated with an increased frequency of KIR2DL1–3+ NK cells. Further analysis showed that KIR2DL1+ NK cells were selectively increased in individuals homozygous for HLA‐C2, while HLA‐C1‐homozygous individuals displayed increased proportions of KIR2DL2/3+ NK cells. KIR2DL1–3+ NK cells were furthermore more polyfunctional during primary HIV‐1 infection in individuals also encoding for their cognate HLA‐C group haplotypes, as measured by degranulation and IFN‐γ and TNF‐α production. These results identify a novel relationship between HLA‐C and KIR2DL+ NK‐cell subsets and demonstrate that HLA‐C‐mediated licensing modulates NK‐cell responses to primary HIV‐1 infection. 相似文献
11.
V. Yu. Umanskii T. E. Klyuchareva V. A. Matveeva 《Bulletin of experimental biology and medicine》1989,107(4):492-494
R. E. Kavetskii Institute for Problems in Oncology, Academy of Sciences of the Ukrainian SSSR, Kiev. Research Institute of Carcinogenesis, All-Union Oncologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Trapeznikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 107, No. 4, pp. 438–440, April, 1989. 相似文献
12.
Tieying Shan Wei Shang Lei Zhang Chunfang Zhao Wei Chen Yanan Zhang Guiying Li 《International journal of clinical and experimental pathology》2015,8(8):8948-8957
Recent studies have shown that angiotensin II (Ang II) or angiotensin-(1-7) [Ang-(1-7)] has effect on the proliferation and activation of a variety of cells, however, the exact mechanisms that the role of Ang II or Ang-(1-7) in human endometrial stromal cell (ESCs) remains elusive. Here we demonstrated that Ang II could promote proliferation and activation of ESCs, up-regulated the expression of a-SMA, TGF-β1 and IGF-I, increased the secretion of extracellular matrix [Type I collagen (Col I) and fibronectin (FN)] of ESCs; Ang-(1-7) could inhibit Ang II induced the proliferation and activation of ESCs, down-regulated the expression of a-SMA, TGF-β1 and IGF-I, decreased the secretion of extracellular matrix (Col I and FN) of ESCs. These findings suggest that Ang-(1-7) can inhibits Ang II induced the proliferation of ESCs, Ang-(1-7) can inhibits the Ang II induced activation of ESCs and decreases secretion of Col I and FN by suppressing TGF-β1 and IGF-I expression. 相似文献
13.
14.
Reciprocal expression of CD70 and of its receptor, CD27, in human long term-activated T and natural killer (NK) cells: inverse regulation by cytokines and role in induction of cytotoxicity
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A M ORENGO C CANTONI F NEGLIA R BIASSONI S FERRINI 《Clinical and experimental immunology》1997,107(3):608-613
15.
Muñoz-Cobo B Solano C Benet I Costa E Remigia MJ de la Cámara R Nieto J López J Amat P Garcia-Noblejas A Bravo D Clari MÁ Navarro D 《Journal of medical virology》2012,84(2):259-267
Immune mechanisms involved in control of cytomegalovirus (CMV) infection in the allogeneic stem cell transplantation setting have not been fully disclosed. CMV pp65 and IE-1-specific CD8(+) T cells expressing IFN-γ, TNF-α, and CD107a, alone or in combination, and NKG2C(+) NK cells were prospectively enumerated during 13 episodes of CMV DNAemia. The expansion of monofunctional and polyfunctional CD8(+) T cells was associated with CMV DNAemia clearance. The size and functional diversity of the expanding CD8(+) T-cell population was greater in self-resolved episodes than in episodes treated with antivirals. These differences were related to the magnitude of expansion of cognate antigen IFN-γ CD4(+) T cells. The resolution of CMV DNAemia was associated frequently with a marked expansion of both CD56(dim) /CD16(+) NK cells and NKG2C(+) CD56(bright) /CD16(-) NK cells. The data lend support to the role of polyfunctional CD8(+) T cells in controlling CMV replication in the allogeneic stem cell transplantation setting, and suggest that NKG2C(+) NK cells may be involved critically in the resolution of CMV DNAemia episodes. 相似文献
16.
Uchimura K Itoh M Yamamoto K Imamura S Makino M Kato T Fujiwara K Sawai Y 《Clinical and experimental immunology》2002,128(2):308-312
The possible roles of CD8+ cells in the abnormal T cell-dependent B-cell activation in Graves' disease were investigated by analysing lymphocyte subsets in peripheral blood mononuclear cells (PBMC) and their production of soluble factors and cytokines such as IL-10 in patients with Graves' disease, Hashimoto's thyroiditis and normal controls. The PBMC were separated into CD8+ and CD8-depleted cells by magnetic separation columns, and cultured for 7 days with or without anti-CD40 monoclonal antibodies and IL-4. The culture supernatant was assayed for sCD23 and IL-10 using EIA, and the remaining cells were analysed by flow cytometry. Stimulation with anti-CD40 antibody together with IL-4 increased sCD23 levels and the number of CD23+ cells. The latter was further augmented by depletion of CD8+ cells. This combination of B cell stimulants increased production of IL-10 by PBMC from patients with Graves' disease. The CD40- and IL-4-activated production of IL-10 was decreased by CD8+ cell depletion. In contrast, constitutive production of IL-10 was increased after CD8+ cell depletion in a group of patients with low basal secretion levels (<35 ng/ml). It was, however, decreased in a group with higher basal production levels, but such a relationship was not found in the normal control group. Thus, T cell-dependent B-cell activation via a CD40 pathway activates CD23+ cells, leading to over-production of IL-10 and a shift of the Th1/Th2 balance to Th2 dominance, while CD8+ cells may suppress this activation to counteract the Th2 deviation in Graves' disease. 相似文献
17.
Murine CD8 lymphocyte expansion in vitro by artificial antigen-presenting cells expressing CD137L (4-1BBL) is superior to CD28, and CD137L expressed on neuroblastoma expands CD8 tumour-reactive effector cells in vivo 总被引:4,自引:0,他引:4
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The ability to expand tumour-infiltrating lymphocytes in vitro has been greatly enhanced by the use of antigen-independent mechanisms of immune cell costimulation. We have produced human, using the K562 cell line, and murine, using YAC-1 cells, artificial antigen presenting cells (aAPC) and demonstrate that these cell types stimulate murine lymphocyte populations in distinct ways. Using aAPC that have been transfected with CD137L (4-1BBL) and CD32 (FcRgammaII), as a means to bind anti-CD3 and anti-CD28 antibody, we found that CD4 cells preferentially expanded in vitro with K562 aAPC, while CD8 cells expanded with both K562 and YAC-1 aAPC. Co-stimulation mediated by CD137L on aAPC was superior to that mediated by anti-CD28 antibody. This was seen in both long and short-term expansion assays, and by the rapid induction of a CD8+ DX5+ population. DX5 serves, under these in vitro conditions, as a general marker for lymphocyte activation. In vivo, the superiority of CD137L was demonstrated by the induction of T helper 1 effectors seen in freshly isolated splenocytes from mice immunized with CD137L-expressing neuroblastoma tumour vaccines. The ability to stimulate a strong CD8 CTL response in vivo correlated with the induction of a DX5+ cell population in splenocytes with a memory-effector phenotype. The presence of this unique DX5+ cell population, phenotypically distinct with regards to CD69 and CD62L expression from DX5+ cells induced by aAPC in vitro, may be associated with the ability of CD137L to induce strong anti-tumour immunity. 相似文献
18.
Alexander Vargas-Hernández Emily M. Mace Ofer Zimmerman Christa S. Zerbe Alexandra F. Freeman Sergio Rosenzweig Jennifer W. Leiding Troy Torgerson Matthew C. Altman Edith Schussler Charlotte Cunningham-Rundles Ivan K. Chinn Alexandre F. Carisey Imelda C. Hanson Nicholas L. Rider Steven M. Holland Jordan S. Orange Lisa R. Forbes 《The Journal of allergy and clinical immunology》2018,141(6):2142-2155.e5
19.
Transcriptional regulation of Hb‐α and Hb‐β through nuclear factor E2‐related factor‐2 (Nrf2) activation in human vaginal cells: A novel mechanism of cellular adaptability to oxidative stress
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Debarchana Saha Swanand Koli Kudumula Venkata Rami Reddy 《American journal of reproductive immunology (New York, N.Y. : 1989)》2017,77(6)
20.
Fanny Legrand Yun Cao Joshua B. Wechsler Xiang Zhu Nives Zimmermann Shakuntala Rampertaap Joseph Monsale Kimberly Romito Bradford A. Youngblood Emily C. Brock Michelle A. Makiya Nenad Tomasevic Christopher Bebbington Irina Maric Dean D. Metcalfe Bruce S. Bochner Amy D. Klion 《The Journal of allergy and clinical immunology》2019,143(6):2227-2237.e10