75 INHIBITION OF NK CELL CYTOTOXICITY IN CLONED MINI-PIGS EXPRESSING HUMAN LEUKOCYTE ANTIGEN-G1 (HLA-G1) GENE

2007 ◽  
Vol 19 (1) ◽  
pp. 155
Author(s):  
K. W. Park ◽  
G. S. Han ◽  
K. M. Choi ◽  
S. P. Hong ◽  
J. Y. Yoo ◽  
...  
Keyword(s):  
Nk Cells ◽  
Cell Lines ◽  
Nk Cell ◽  
Control Group ◽  
Cell Cytotoxicity ◽  
Xenograft Rejection ◽  
Clonal Cell ◽  
Fetal Fibroblasts ◽  
Clonal Cell Lines ◽  
Mini Pigs

Human natural killer (NK) cell-mediated response plays an important role in xenograft rejection. In the case of pig-to-human xenotransplantation, it has been suggested that NK cells are involved in delayed-type rejection, which is characterized by pig endothelial cell (pEC) activation, direct lysis, and secretion of proinflammatory cytokines. NK cell activation can be a direct barrier to the potential use of pig organs for human xenograft transplantation. Therefore, it is important to suppress the NK cell activity on pig-to-human xenografts. Expression of HLA-G1 (non-classical major histocompatibility complex class I molecules) inhibits the cytotoxic activity of NK cells and has been proposed as a potential solution to overcome NK cell-mediated xenogeneic cytotoxicity in pEC. In this study, we transfected the HLA-G1 gene into mini-pig fetal fibroblasts to produce 2 HLA-G1 clonal cell lines. These cell lines were used to produce cloned HLA-G1 transgenic mini-pigs by nuclear transfer (NT). The presence of the HLA-G1 gene in transgenic mini-pigs was confirmed by PCR. The expression of HLA-G1 was detected by flow cytometry-immunohistochemistry assay. Mini-pig fibroblasts derived from a 35-day-old cloned fetus also showed characteristics similar to those of HLA-G1 clonal cell lines. The expressed HLA-G1 significantly suppressed NK-mediated cell lysis, and the rate of NK 92MI cell cytotoxicity was reduced as compared to the control group (HLA-G1: 46.7 � 4.5%; control: 4.6 � 13.3%; P < 0.05). In conclusion, transgenic cloned mini-pigs expressing HLA-G1 were produced by NT for the first time. It is expected that these mini-pigs could be used to overcome the NK cell-mediated rejection in xenotransplantation.

184 INHIBITION OF HUMAN COMPLEMENT-MEDIATED CYTOTOXICITY IN MINIPIG CELLS BY EXPRESSION OF hCD59

2008 ◽  
Vol 20 (1) ◽  
pp. 172
Author(s):  
K. W. Park ◽  
E. J. Kim ◽  
K. M. Choi ◽  
S. P. Hong ◽  
G. S. Han ◽  
...  
Keyword(s):  
Cell Lines ◽  
Membrane Attack Complex ◽  
Inhibitory Effect ◽  
Negative Control ◽  
Control Group ◽  
Human Complement ◽  
Transgenic Pigs ◽  
Clonal Cell ◽  
Fetal Fibroblasts ◽  
Clonal Cell Lines

Xenotransplantation of a pig organ to a human is a possible solution for the shortage of donor organs for transplantation. However, hyperacute rejection (HAR) due to natural antibodies (Nab) present major obstacle in pig-to-human xenotransplantation. To overcome this, much effort has been dedicated to preparing transgenic pigs that express human complement regulatory proteins (CRPs). One of CRPs, the human CD59 gene, can prevent the terminal polymerization of the membrane attack complex by complement. In this study, we investigated the inhibitory effect of hCD59 on complement-mediated cytotoxicity in hCD59-transfected minipig cells. To generate cell lines expressing hCD59, we transfected the hCD59 gene into minipig fetal fibroblasts and established seven transgenic clonal cell lines. The integration of hCD59 gene was confirmed by PCR and expression levels were measured by RT-PCR, fluorescence-activated cell sorting (FACS), Western blot, and immunohistochemistry. FACS analysis of hCD59 clonal cell lines demonstrated a substantial increment of hCD59 expression. The level (82% to 95%) of hCD59 protein expression was increased relative to that of the control. Human complement-mediated cytotoxicity was measured using a CytoTox96� (Promega Corp., Sydney, Australia) non-radioactive cytotoxicity (LDH) assay using normal minipig cells as a negative control. In the LDH release assay, human complement-mediated cytotoxicity was also significantly reduced to 39.6 � 17.8% in comparison to that of the control group (73.6 � 19.1%; P < 0.05; n = 6). These results indicate that the expression of hCD59 gene in minipig cells can efficiently control complement-mediated cytotoxicity.

scholarly journals Pharmacologic inhibition of lysine-specific demethylase 1 as a therapeutic and immune-sensitization strategy in pediatric high-grade glioma

2020 ◽  
Vol 22 (9) ◽  
pp. 1302-1314 ◽  
Author(s):  
Cavan P Bailey ◽  
Mary Figueroa ◽  
Achintyan Gangadharan ◽  
Yanwen Yang ◽  
Megan M Romero ◽  
...  
Keyword(s):  
Nk Cells ◽  
Cell Lines ◽  
Nk Cell ◽  
Gene Signature ◽  
Immune Gene ◽  
High Grade ◽  
Cell Cytotoxicity ◽  
Lysine Specific Demethylase

Abstract Background Diffuse midline gliomas (DMG), including brainstem diffuse intrinsic pontine glioma (DIPG), are incurable pediatric high-grade gliomas (pHGG). Mutations in the H3 histone tail (H3.1/3.3-K27M) are a feature of DIPG, rendering them therapeutically sensitive to small-molecule inhibition of chromatin modifiers. Pharmacological inhibition of lysine-specific demethylase 1 (LSD1) is clinically relevant but has not been carefully investigated in pHGG or DIPG. Methods Patient-derived DIPG cell lines, orthotopic mouse models, and pHGG datasets were used to evaluate effects of LSD1 inhibitors on cytotoxicity and immune gene expression. Immune cell cytotoxicity was assessed in DIPG cells pretreated with LSD1 inhibitors, and informatics platforms were used to determine immune infiltration of pHGG. Results Selective cytotoxicity and an immunogenic gene signature were established in DIPG cell lines using clinically relevant LSD1 inhibitors. Pediatric HGG patient sequencing data demonstrated survival benefit of this LSD1-dependent gene signature. Pretreatment of DIPG with these inhibitors increased lysis by natural killer (NK) cells. Catalytic LSD1 inhibitors induced tumor regression and augmented NK cell infusion in vivo to reduce tumor burden. CIBERSORT analysis of patient data confirmed NK infiltration is beneficial to patient survival, while CD8 T cells are negatively prognostic. Catalytic LSD1 inhibitors are nonperturbing to NK cells, while scaffolding LSD1 inhibitors are toxic to NK cells and do not induce the gene signature in DIPG cells. Conclusions LSD1 inhibition using catalytic inhibitors is selectively cytotoxic and promotes an immune gene signature that increases NK cell killing in vitro and in vivo, representing a therapeutic opportunity for pHGG. Key Points 1. LSD1 inhibition using several clinically relevant compounds is selectively cytotoxic in DIPG and shows in vivo efficacy as a single agent. 2. An LSD1-controlled gene signature predicts survival in pHGG patients and is seen in neural tissue from LSD1 inhibitor–treated mice. 3. LSD1 inhibition enhances NK cell cytotoxicity against DIPG in vivo and in vitro with correlative genetic biomarkers.

scholarly journals Suppression of Natural Killer Cell Cytotoxicity in Postpartum Women

2013 ◽  
Vol 16 (3) ◽  
pp. 320-326 ◽  
Author(s):  
Maureen W. Groer ◽  
Nagwa El-Badri ◽  
Julie Djeu ◽  
S. Nicole Williams ◽  
Bradley Kane ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Postpartum Period ◽  
Nk Cell ◽  
Killer Cell ◽  
Control Group ◽  
Postpartum Women ◽  
Cell Cytotoxicity ◽  
Natural Killer Cell Cytotoxicity ◽  
Nk Cytotoxicity

Little is known about the recovery of the immune system from normal pregnancy and whether the postpartum period is a uniquely adapted immune state. This report extends previous observations from our group of decreased natural killer (NK) cell cytotoxicity in the postpartum period. NK cytotoxicity was measured from 1 week through 9 months postpartum. In addition, NK cytotoxicity was assayed in the presence or absence of pooled plasmas collected from either postpartum or nonpostpartum women. Samples of cells were stained for inhibitory receptors and analyzed by flow cytometry. NK cytotoxicity remained decreased in postpartum women compared to controls through the first 6 postpartum months, returned to normal levels by 9 months, and remained normal at 12 months. NK cytotoxicity during the first 6 months was further inhibited by the addition of pooled plasma to NK cultures from postpartum women, but the addition of pooled plasma from the control group did not affect that group’s NK cultures. There were differences in inhibitory receptor staining between the two groups, with decreased CD158a and CD158b and increased NKG2A expression on postpartum NK cells during the first 3 postpartum months. These data suggest that NK cytotoxicity postpartum inhibition lasts 6 months and is influenced by unidentified postpartum plasma components. The effect may also involve receptors on NK cells.

scholarly journals Generation of myostatin edited horse embryos using CRISPR/Cas9 technology and somatic cell nuclear transfer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lucia Natalia Moro ◽  
Diego Luis Viale ◽  
Juan Ignacio Bastón ◽  
Victoria Arnold ◽  
Mariana Suvá ◽  
...  
Keyword(s):  
Somatic Cell ◽  
Cell Lines ◽  
Somatic Cell Nuclear Transfer ◽  
Nuclear Transfer ◽  
Negative Regulator ◽  
Dependent Manner ◽  
Myostatin Gene ◽  
Clonal Cell ◽  
Fetal Fibroblasts ◽  
Clonal Cell Lines

Abstract The application of new technologies for gene editing in horses may allow the generation of improved sportive individuals. Here, we aimed to knock out the myostatin gene (MSTN), a negative regulator of muscle mass development, using CRISPR/Cas9 and to generate edited embryos for the first time in horses. We nucleofected horse fetal fibroblasts with 1, 2 or 5 µg of 2 different gRNA/Cas9 plasmids targeting the first exon of MSTN. We observed that increasing plasmid concentrations improved mutation efficiency. The average efficiency was 63.6% for gRNA1 (14/22 edited clonal cell lines) and 96.2% for gRNA2 (25/26 edited clonal cell lines). Three clonal cell lines were chosen for embryo generation by somatic cell nuclear transfer: one with a monoallelic edition, one with biallelic heterozygous editions and one with a biallelic homozygous edition, which rendered edited blastocysts in each case. Both MSTN editions and off-targets were analyzed in the embryos. In conclusion, CRISPR/Cas9 proved an efficient method to edit the horse genome in a dose dependent manner with high specificity. Adapting this technology sport advantageous alleles could be generated, and a precision breeding program could be developed.

302 INHIBITION OF HUMAN NATURAL KILLER (NK) CELL-MEDIATED CYTOTOXICITY IN MINIPIG CELLS BY KAPOSI'S SARCOMA-ASSOCIATED HERPESVIRUS K5 PROTEIN

2008 ◽  
Vol 20 (1) ◽  
pp. 231
Author(s):  
G. S. Han ◽  
K. M. Choi ◽  
S. P. Hong ◽  
J. Y. Yoo ◽  
E. J. Kim ◽  
...  
Keyword(s):  
Natural Killer ◽  
Cell Lines ◽  
Kaposi's Sarcoma ◽  
Cell Activation ◽  
Nk Cell ◽  
Kaposi’S Sarcoma ◽  
Xenograft Rejection ◽  
Fetal Fibroblasts ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

Human natural killer (NK) cell-mediated response plays an important role in xenograft rejection. In the case of pig-to-human xenotransplantation, it has been suggested that NK cells are involved in delayed-type rejection, which is characterized by pig endothelial cell activation, direct lysis, and secretion of proinflammatory cytokines. Natural killer cell activation can be a direct barrier to the potential use of pig organs for human xenograft transplantation. Therefore, it is important to suppress NK cell activity on pig-to-human xenografts. Expression of Kaposi's sarcoma-associated herpesvirus (KSHV)-K5 molecules inhibits the cytotoxic activity of NK-activating receptor (B7-2, ICAM-1). As a consequence, K5 expression drastically inhibits NK cell-mediated cytotoxicity. In this study, we produced cell lines expressing K5 to control NK-mediated cytotoxicity in minipig cells. We transfected the K5 gene into minipig fetal fibroblasts and established 2 transgenic clonal cell lines. Presence of the K5 gene was confirmed by PCR, and expression of the gene was identified by real-time PCR and flow cytometry. In an NK cytotoxicity assay, the rate of NK-92MI-mediated cytotoxicity was significantly reduced, to 48.4 � 5.9% compared with the control (75.6 � 5.8%; P < 0.05, n = 8, paired t-testing). In conclusion, these results indicate that the expression of K5 molecules on porcine cells can efficiently control NK-mediated cytotoxicity. This strategy can be used in transgenic pig production in which porcine organs would be protected from NK-mediated rejection.

276 PRODUCTION OF TRANSGENIC MINI-PIG CELL LINES EXPRESSING HUMAN CYTOMEGALOVIRUS US2

2007 ◽  
Vol 19 (1) ◽  
pp. 254
Author(s):  
K. W. Park ◽  
J. Y. Yoo ◽  
K. M. Choi ◽  
S. P. Hong ◽  
G. S. Han ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cytomegalovirus ◽  
Recombinant Expression ◽  
Class I ◽  
Class I Mhc ◽  
Specific Lysis ◽  
Clonal Cell ◽  
Fetal Fibroblasts ◽  
Clonal Cell Lines

Xenotransplantation has the potential to resolve the chronic shortage of donor organs if immunological barriers can be overcome. In particular, the initial type of rejection following xenotransplantation is acute cellular rejection by host CD8+ cytotoxic T lymphocyte (CTL) cells that react to the donor class I major histocompatibility complex (MHC). The human cytomegalovirus (HCMV) glycoprotein US2 specifically targets class I MHC heavy chains for dislocation from the endoplasmic reticulum (ER) membrane to the cytosol, where they are degraded by the proteasome. In this study, the recombinant expression vector pCX-US2 was stably transfected into mini-pig fetal fibroblasts by lipofection. The integration of US2 into the host genome was confirmed by PCR and Southern blot assay. The reduction of swine leukocyte antigen class I (SLA-I, MHC protein class I) by US2 was detected by flow cytometry analysis (FACS). FACS analysis of US2 clonal cell lines demonstrated substantial reductions in SLA surface expression. The decrease in the level of class I MHC expression for US2 clonal cell lines ranged from 22 to 34% relative to the non-transfected control. US2 clonal cell lines were also tested to determine if the resulting reduction in cell surface SLA would reduce in vitro cytotoxicity by CTL. The US2 clonal cell line demonstrated 5- to 6-fold reduction of specific lysis by primed CD8+ CTL. In conclusion, US2 can directly protect pig clonal cell lines from human CTL cells. These results indicate that the expression of US2 in pig cells may provide a new approach toward overcoming CTL-mediated immunity to xenotransplantation. This work was supported by the National Livestock Research Institute (6132-211-303-1).

193 HUMAN CYTOMEGALOVIRUS PROTEIN US11 DOWN-REGULATES THE EXPRESSION OF SWINE LEUKOCYTE ANTIGEN-I IN MINIPIG CELLS

2008 ◽  
Vol 20 (1) ◽  
pp. 176
Author(s):  
J. Y. Yoo ◽  
K. M. Choi ◽  
S. P. Hong ◽  
G. S. Han ◽  
E. J. Kim ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cytomegalovirus ◽  
Cytotoxic T Lymphocyte ◽  
Early Stage ◽  
Swine Leukocyte Antigen ◽  
Leukocyte Antigen ◽  
Clonal Cell ◽  
Heavy Chains ◽  
Fetal Fibroblasts ◽  
Clonal Cell Lines

The CD8+ cytotoxic T lymphocyte (CTL)-mediated immune response is important in porcine xenotransplantation, and pigs could be used as a good model for organ donor if these immunological barriers are overcome. Human cytomegalovirus (HCMV) encodes unique short (US) 11 gene, which interferes with cellular immune responses by inducing rapid degradation of newly synthesized heavy chains of major histocompatibility (MHC) class I. The destruction of heavy chains by US11 helps the virus to hide from recognition by cytotoxic T lymphocytes at early stage. In this study we demonstrated the inhibitory effect of US11 on the cytotoxicity of CTL cells by down-regulation of swine leukocyte antigen (SLA)-I expression. We established five US11 clonal cell lines by transfection into minipig fetal fibroblasts and confirmed the integration of US11 gene by PCR and Southern blot assay. The reduction of SLA-I, which was expressed on the cell surface, was also detected by flow cytometry assay. The level (14.6% to 21.2%) of SLA-1 expression in US11 clonal cell lines was decreased relative to that in the control. In the CTL assay, the rate of CD8+ T cell-mediated cytotoxicity was significantly reduced to 31.9 � 11.3%, compared to that of the control (81.4 � 5.3%; P < 0.01; n = 4). These results indicate that HCMV viral protein US11 can effectively suppress the presentation of SLA-I in pig fetal fibroblast cells. This work was supported by a grant (Code # 20070101034005) from the BioGreen 21 Program, Rural Development Administration, Republic of Korea.

Mimicking An Induced Self Phenotype by Coating Lymphomas with the Nkp30-Ligand B7-H6 Promotes Antitumoral Natural Killer Cell Cytotoxicity

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 103-103
Author(s):  
Christian Kellner ◽  
Tina Maurer ◽  
Daniela Hallack ◽  
Roland Repp ◽  
Jan G.J. van de Winkel ◽  
...  
Keyword(s):  
Cell Surface ◽  
Fusion Protein ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Cell Lines ◽  
Surface Density ◽  
Nk Cell ◽  
Cell Cytotoxicity ◽  
Nk Cell Cytotoxicity

Abstract Abstract 103 Induced self-expression of ligands for stimulatory receptors facilitates natural killer (NK) cell-mediated elimination of stressed cells. Stimulatory receptors include Natural killer group 2 member D (NKG2D) and Nkp30, which control cytotoxic activities of NK cells and are important in immune surveillance against tumors. Specific modulation of NK cell cytotoxicity by selectively increasing the surface density of activating ligands on tumor cells may therefore represent an innovative approach to develop novel treatment strategies. A novel fusion protein was designed to enhance NK cell-based immune responses against B-lineage lymphomas by increasing the cell surface density of the recently identified Nkp30 ligand B7-H6 on tumor cells. The recombinant protein consisted of the ectodomain of B7-H6 and a CD20-directed human single chain fragment variable (scFv) as targeting device. The resulting fully-human protein designated B7-H6:CD20-scFv was eukaryotically expressed and purified by affinity chromatography. B7-H6:CD20-scFv indeed had bifunctional properties as reflected by its ability to simultaneously bind to the CD20 antigen and to the Nkp30 receptor. CD20-positive lymphoma cells opsonized with B7-H6:CD20-scFv alerted human NK cells as indicated by upregulated surface expression levels of the early inducible activation marker CD69. Activation was accompanied by induced CD107a cell surface exposure indicating enhanced NK cell degranulation. In cytotoxicity assays using human NK cells from healthy donors as effector cells, B7-H6:CD20-scFv triggered killing of lymphoma-derived B-cell lines. B7-H6:CD20-scFv was active in a strictly antigen-specific manner as demonstrated by blocking experiments and was not able to mediate killing of cell lines not expressing the CD20 target antigen. B7-H6:CD20-scFv mediated killing of lymphoma cells in a dose-dependent manner starting at nanomolar concentrations. Target cell death induced by B7-H6:CD20-scFv occurred by apoptosis and involved caspase cleavage. Moreover, B7-H6:CD20-scFv induced NK cell-mediated lysis of fresh tumor cells from 8/8 CLL and 5/5 MCL patients with variable CD20 expression levels. In comparison to ULBP2:CD20-scFv, a similarly constructed fusion protein of the NKG2D ligand ULBP2 and a CD20-directed scFv, the B7-H6:CD20-scFv had a lower potency (EC50 values for B7-H6:CD20-scFv and ULBP2:CD20-scFv were 100 and 4 nM, respectively) but nevertheless achieved similar maximum extents of lysis. Interestingly, when B7-H6:CD20-scFv was added together with ULBP2:CD20-scFv to a mixture of NK cells and target cells, synergistic cytotoxic effects were induced. The combined treatment resulted in a higher percentage of NK cells that responded and exposed the degranulation marker CD107a on the cell surface in comparison to samples containing only one of the two agents. As a consequence a significantly higher extent of lysis was achieved. These results strongly indicate a co-operation between Nkp30 and NKG2D signalling which use different downstream signalling pathways. Thus, mimicking an induced self phenotype of tumors by coating lymphomas with B7-H6:CD20-scFv either alone or in combination with molecules triggering NKG2D may provide an innovative strategy to enhance specific anti-tumoral NK cell cytotoxicity. Disclosures: van de Winkel: Genmab: Employment. Parren:Genmab BV: Employment. Peipp:Genmab: Consultancy.

Impaired NK cell cytotoxicity by high level of interferon-γ in concanavalin A-induced hepatitis

2005 ◽  
Vol 83 (11) ◽  
pp. 1045-1053 ◽  
Author(s):  
Zhongjun Dong ◽  
Cai Zhang ◽  
Haiming Wei ◽  
Rui Sun ◽  
Zhigang Tian
Keyword(s):  
Nk Cells ◽  
Cell Lines ◽  
Nk Cell ◽  
Interferon Γ ◽  
Cell Cytotoxicity ◽  
Wild Mice ◽  
Ifn Γ ◽  
Nk Cell Cytotoxicity

Unlike T cells, the role of natural killer (NK) cells is not well documented in the concanavalin (ConA)- induced hepatitis model. This study aimed to investigate the regulatory effect of high levels of interferon-γ (IFN-γ) on NK cells in ConA-induced hepatitis. The cytotoxicities of NK cells from ConA-injected mice or NK cell lines (NK92 and NKL) were detected by the 4-h 51Cr release assay. Depletion of NK cells with AsGM1 antibody was used to assess the NK cell role in ConA-induced hepatitis. Expression of NK cell receptors and cytotoxic molecules was measured by reverse transcription – polymerase chain reaction. Twelve hours after ConA injection, serum IFN-γ was significantly increased in wild mice, but not in severe combined immunodeficiency mice, and hepatic NK cells exerted impaired cytotoxicity against YAC-l cells in wild mice. Eight hours after NK cells were incubated in serum from ConA-treated mice, NK cell cytotoxicity was down-modulated and the effect was abolished by pretreatment with neutralizing serum IFN-γ with specific antibody in vitro. A high concentration of IFN-γ (> 1000 U/mL) inhibited the cytotoxicities of 2 NK cell lines in vitro, accompanied with down-regulation of NKG2D transcripts and up-regulation of NKG2A/B and KIR2DL transcripts. The inhibitive role of IFN-γ was not seen in NKG2D ligand negative cells. These results suggest that NK cell cytotoxicity was inhibited by high levels of IFN-γ in ConA-induced hepatitis, which may relate to the dispensable role of NK cells.Key words: cytotoxicity, hepatoimmunology, interferon-γ, liver injury.

scholarly journals Familial cancer: depressed NK-cell cytotoxicity in healthy and cancer affected members

2001 ◽  
Vol 59 (1) ◽  
pp. 6-10 ◽  
Author(s):  
Terezinha C.B. Montelli ◽  
Maria Terezinha S. Peraçoli ◽  
Roberto C. Gabarra ◽  
Angela M.V.C. Soares ◽  
Cilmery Suemi Kurokawa
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Familial Cancer ◽  
Family Members ◽  
Cell Activity ◽  
T Cell Subsets ◽  
Control Group ◽  
Target Cells ◽  
Cell Cytotoxicity ◽  
Nk Cell Cytotoxicity

Depressed natural killer (NK) cell activity has been showed in family members of patients with different types of cancer. The present work aimed to evaluate T cell subsets and NK cell cytotoxic activity in 15 members of a family with high incidence of tumors, such as glioblastoma, gastric, pancreas and colon rectal carcinoma, chronic myelocitic leukemia, melanoma and osteoblastoma. As controls, 19 healthy subjects with the age range equivalent were studied. The enumeration of CD3+ lymphocytes and their CD4+ and CD8+ subsets were defined by monoclonal antibodies and NK cell cytotoxicity towards K562 target cells were evaluated by single cell-assay. The results showed in family members low percentage of total T cells (CD3+), and their CD4+ subset and impairment of CD4/CD8 ratio in relation to control group. All family members presented percentage of NK-target cell conjugate formation bellow the minimum value observed in control group. Thirteen people were examined and followed up during five years, in order to assure that there was no undiagnosed or unsuspected disease at the moment of evaluation. One of them developed osteoblastoma and other malignant melanoma. Two cancer patients, with glioblastoma and chronic myelocytic leukemia were studied during illness. All the corresponding values were comparable. The persistence of low percentage of conjugate formation may be related to a defect on adhesion molecules expression in the surface of NK cells that was probably responsible for the low activity of these cells presented by the family group. Thus, the inheritance mechanism of low adherence of NK cells should have a prognostic value in determining the risk of developing tumors.

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