Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CD69 Antigens”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2003

The use of transgenic mice for the production of a human monoclonal antibody specific for human CD69 antigen.

The CD69 antigen is the earliest activation marker expressed on leukocyte surfaces after stimulation and it has been correlated with disease state in a variety of inflammatory and autoimmune diseases. We were interested in the generation of a human monoclonal antibody (mAb) against the CD69 antigen. To do this, mice carrying human Ig transgenes (on an inactivated endogenous immunoglobulin H and Igkappa background) were immunized with rat cells transfected with the human CD69 molecule. From over 2000 hybridoma clones generated in different fusions, we were able to obtain a human monoclonal antibody, hAIM-29, which specifically recognizes human CD69 on the surface of activated-human leukocytes. We demonstrate that the antibody is specific for the human CD69 molecule, as shown by double staining with mouse anti-human CD69 antibodies, ELISA, immunoblot and immunoprecipitation studies. Results of additional experiments show that hAIM-29 activates intracellular calcium influx without Ig cross-linking and enhances phorbol myristate acetate-induced cell proliferation in a manner similar to other mouse anti-CD69 antibodies. This report is the first to describe the isolation and characterization of a novel human mAb, hAIM-29, which may have therapeutic potential in diseases associated with the presence of activated cells expressing CD69 antigen.

Animals↗
PubMed2004

Induction of CD69 antigen expression in peripheral blood mononuclear cells on exposure to silica, but not by asbestos/chrysotile-A.

While cases of silicosis are often complicated by various autoimmune disorders, patients with asbestosis develop malignant tumors such as lung cancer and malignant mesothelioma. These differences may derive from different biological effects, particularly on immunological cells, of silica and asbestos. To find differences between silica and asbestos, the early activation antigen, CD69, on T cells was examined because dysregulated and continuous activation of T cells may promote the survival of self-recognizing T cells. After cultivation of peripheral blood mononuclear cells with or without silica or chrysotile-A, an asbestos, only silica induced CD69 expression on the lymphocytes. This induction of CD69 expression was mediated by protein kinase C activation. In addition, cell-cell contact mediated by HLA-DR was more important than soluble factors secreted from silica-phagocytosed cells such as IL-1beta, IL-6, and IL-8, even though IL-6 and IL-8 were produced during the culture of PBMCs with silica and chrysotile-A. It should be examined how these activated, CD69-expressing lymphocytes affect other immune systems as well as alter themselves in terms of cytokine production and cell-cell interaction, leading to autoimmune disorders in silicosis patients.

Antibodies↗
PubMed1996

Unresponsiveness of CD4+ T cells from a non-responder strain to HgCl2 is not due to CD8(+)-mediated immunosuppression: an analysis of the very early activation antigen CD69.

Injections of HgCl2 lead to autoimmune manifestations in genetically predisposed rats and mice. In this study, the authors examined the responsiveness of T subsets from different mouse strains to HgCl2 by tracing their expression of the very early activation antigen CD69. The authors found increased expression of the CD69 antigen on CD4+ T cells from the responder A.SW and BALB/c mice, but not on CD4+ T cells from the non-responder DBA/2 mice, indicating an activation of T helper cells in the responder strains. However, the CD69 antigen was induced on CD8+ T cells from all strains irrespective whether they were susceptible or resistant to mercury-induced autoimmunity. Since CD8+ T cells have been described as mediating immunosuppression and as being responsible for the resistance to autoimmune induction by mercury, the authors tested whether CD8+ T cells inhibited the activation of CD4+ T cells by HgCl2 in the non-responder strains. However, there was no evidence for a suppressive role of CD8+ T cells from the DBA/2 mice in the response to HgCl2. The findings indicate that T helper cells play a central role in the immunological effects of HgCl2 and unresponsiveness of T helper cells in the nonresponder strains is not due to CD8(+)-mediated immunosuppression.

Animals↗
PubMed1993

[Expression of activation antigen CD69 on eosinophils].

The antigen, CD69, has been shown to be expressed on activated lymphocytes. CD69 has also been shown to be associated with signal transduction process. Recently, we demonstrated the expression of CD69 on eosinophils at inflammatory sites. Whatever the disease, lung eosinophils obtained from the bronchoalveolar lavage fluid or pleural effusion expressed significant levels of CD69, whereas most peripheral blood (PB) eosinophils did not express CD69. Further, in vitro stimulation of PB eosinophils by IL-3, IL-5, GM-CSF and PMA induced CD69 expression on PB eosinophils. These findings suggest that CD69 expression on eosinophils is restricted to local inflammatory sites and CD69 may be a useful marker for activated eosinophils at inflammatory sites.

Antigens, CD↗
PubMed1993

Differential effects of tyrosine kinase inhibition in CD69 antigen expression and lytic activity induced by rIL-2, rIL-12, and rIFN-alpha in human NK cells.

The effect of rIL-12 on induction of CD69 antigen expression and cytolytic activity in purified human NK cells was evaluated in comparison to the effects of rIL-2 and rIFN-alpha. It was found that rIL-12 directly induced CD69 antigen expression in NK cells, although the period of incubation required by rIL-12 was longer than the period required by rIL-2 or by rIFN-alpha. Similarly, the cytolytic activity induced by rIL-12 in NK cells against the NK-resistant target cell line Raji was consistently lower than the cytolytic activity induced by rIL-2 or rIFN-alpha when measured after 6 hr of incubation, and increased during the following 18 hr of incubation. To compare the involvement of tyrosin kinases in activation of NK cells induced by rIL-2, rIL-12, and rIFN-alpha, the effect of the specific inhibitor of tyrosin kinases, genistein, was evaluated on induction of CD69 antigen expression and lytic function mediated by the three cytokines. It was found that genistein inhibited CD69 antigen expression induced by rIL-2 and by rIL-12, but not that induced by rIFN-alpha. Unlike the effect on CD69 antigen expression, the cytolytic activity induced by all three cytokines was inhibited by genistein. These results, together with the finding that CD69 antigen expression induced by rIL-2 but not by rIL-12 or rIFN-alpha was inhibited by addition of rIL-4, strongly suggest that IL-2, IL-12, and IFN-alpha mediate their effects, leading to induction of CD69 antigen expression through different activation pathways.

Antigens, CD↗
PubMed1993

Molecular characterization of the early activation antigen CD69: a type II membrane glycoprotein related to a family of natural killer cell activation antigens.

CD69 is a disulfide-linked homo-dimer expressed on the surface of activated T cells, B cells, natural killer cells, neutrophils and platelets. Antibody crosslinking of CD69 in the presence of phorbol ester results in cellular activation events including proliferation and the induction of specific genes. Using an expression cloning strategy we have isolated cDNA encoding human CD69 from a CD4+ T cell clone. Transfection of the cDNA clone in CV-1/EBNA cells results in the expression of a covalently linked homodimer. The cDNA insert hybridizes to a 1.7-kb mRNA in phorbol 12-myristate 13-acetate- or phytohemoagglutinin-stimulated human T cells. Using the human clone we have isolated cDNA encoding mouse CD69, which, when expressed in human T cells allowed those cells to respond to anti-mouse CD69 antibodies by secreting interleukin-2 and interferon-gamma. Sequence analysis showed that both mouse and human CD69 are type II membrane glycoproteins related to the NKR-P1 and Ly-49 families of natural killer cell activation molecules.

Amino Acid Sequence↗
PubMed1992

Different sensitivity to interleukin 4 of interleukin 2- and interferon alpha-induced CD69 antigen expression in human resting NK cells and CD3+, CD4-, CD8- lymphocytes.

The effect of rIL-4 on CD69 antigen expression induced by rIL-2 or by rINF-alpha on human resting NK cells and CD3+, CD4-, CD8- T lymphocytes has been investigated. rIL-4 drastically inhibited CD69 antigen expression induced by rIL-2 in both cell types. In contrast, rIL-4 did not alter rINF-alpha-induced CD69 antigen expression. Consistent results were obtained evaluating the cytolytic activity of NK cells against the Raji target cell line: rINF-alpha-induced lytic activity was not inhibited by rIL-4, while rIL-2-induced lytic activity was drastically inhibited. Proliferative activity of NK cells induced by rIL-2, in contrast, was only slightly reduced by rIL-4. rIL-4 did not alter the expression of the beta chain of IL-2 receptor, evaluated in NK cells by indirect immunofluorescence. Expression of the alpha chain of IL-2 receptor could not be detected in NK cells by indirect immunofluorescence. It can therefore be suggested that the selective inhibitory effect of rIL-4 on rIL-2-induced activation of NK cells is not mediated by downregulation of alpha and beta chains of IL-2 receptor.

Antigens, CD↗
PubMed2006

[Comparative analysis of CD56 lymphocytes and CD69 antigen expression in endometrium during decidualization].

INTRODUCTION: The exceptionality of endometrium, differentiating it from other epithelial tissues is related with its ability to regulate the number and activity of infiltrating immunological cells according to menstrual cycle phases. The aim of this study was a comparative evaluation of the number of CD56 positive cells, as well the analysis of CD69 antigen expression during decidualization. MATERIALS AND METHODS: The expression of CD56 and CD69 antigens was analyzed using the immunohistochemistry method in 20 decidual tissue samples derived after curettage following spontaneous abortion and in 38 endometrial tissue samples obtained during hysterectomy performed because of benign myoma diagnosis. The endometrial tissue samples were divided regarding to the menstrual cycle phases. Following phases were distinguished: early proliferative, mid-proliferative, late proliferative, early secretory, mid secretory and late secretory. RESULTS: The higher CD56 positive cells were recognized in the endometrium during mid secretory cycle phase. The number of CD56 positive cells was significantly lower in endometrium, independent of menstrual cycle phase in comparison to endometrium following abortion. The expression of CD69 antigen was observed to increase beginning with early secretory cycle phase and remained at high level during the secretory cycle phase and the abortion. CONCLUSIONS: The observed differences in the number of CD56 positive cells during decidualization without the changes in immune cells activity evaluated using CD69 antigen expression may indicate the participation of activated mononuclear cells in the normal development of pregnancy beginning with implantation.

Abortion, Spontaneous↗
PubMed1993

Expression of CD69 antigen on synovial fluid T cells in patients with rheumatoid arthritis and other chronic synovitis.

OBJECTIVES: The expression of the CD69 antigen on synovial fluid and peripheral blood lymphocytes was studied in 12 patients with rheumatoid arthritis (RA), five subjects with other forms of chronic synovitis, and on the peripheral blood lymphocytes of 15 patients with systemic lupus erythematosus (SLE) and immune vasculitis. METHODS: The CD69 antigen and other activation markers (HLA-DR, interleukin 2 receptor (IL-2R), transferrin receptor) were measured by cytometric analysis. In patients with RA soluble IL-2R was determined by enzyme linked immunosorbent assay (ELISA). RESULTS: The percentage of T cells bearing CD69 was significantly increased in synovial fluid from patients with RA (30.3 (13)%) and other chronic synovitis (18 (9)%). The expression of CD69 on peripheral blood lymphocytes of patients with RA, other chronic synovitis, and SLE and immune vasculitis was within the normal range 2.1 (1.2)%. According to previously published work, a high proportion of synovial fluid T cells are HLA-DR positive (64.2 (12.4)% in synovial fluid from patients with RA and 61 (1.2)% in synovial fluid from patients with other chronic synovitis). Transferrin receptor expression on synovial fluid was up-regulated compared with that on peripheral blood. The increase of IL-2R expression on synovial fluid lymphocytes v peripheral blood was not significant; the quantitative determination of soluble IL-2R levels gave a mean value of 921 (351) U/ml in synovial fluid of patients with RA, 672 (229) U/ml in the serum of the same patients, and 273 (100) U/ml in serum from normal subjects. CONCLUSIONS: Synovial fluid lymphocytes are in a different functional state than peripheral blood lymphocytes. CD69 antigen is an interesting cellular marker which should be studied in patients with chronic synovitis. The unusual expression of the activation antigens and the sequence of their appearance require further study.

Antigens, CD↗
PubMed1994

[Expression of activation antigen, CD69, on human local eosinophils].

The activation antigen, CD69, has been shown to be expressed on activated lymphocytes. CD69 has also been shown to be associated with the signal transduction process. Recently, we demonstrated the expression of CD69 on lung eosinophils obtained from the bronchoalveolar lavage fluid of patients with eosinophilic pneumonia. In this study, we performed flowcytometric analysis of CD69 expression on eosinophils obtained from the bronchoalveolar lavage fluid, pleural effusion or peripheral blood of various patients. Whatever the disease, local eosinophils expressed significant levels of CD69, whereas most peripheral blood eosinophils did not express CD69. These findings suggest that CD69 is a marker for local eosinophils and that local eosinophils may differ functionally from peripheral blood eosinophils.

Adult↗
PubMed1997

Rapid expression of the CD69 antigen on T cells and natural killer cells upon antigenic stimulation of peripheral blood mononuclear cell suspensions.

The CD69 antigen has been identified as the earliest activation marker on the surface of cytokine- or mitogen-activated lymphocytes. The expression of this molecule may be a useful early marker of antigen- or allergen-specific activation of lymphocytes in vitro. We evaluated the expression of the CD69 and CD25 antigens on antigen- or allergen-stimulated lymphocytes and the proliferative responses as detected by thymidine incorporation. Peripheral blood mononuclear cells (PBMC) of allergic patients sensitized to Dermatophagoides pteronyssinus, bovine casein, or nickel sulfate were cultured in the absence or presence of clinically relevant allergens, tetanus toxoid, or recombinant interleukin (IL)-2. The respective binding of CD69 or CD25 antibodies to PBMC and thymidine incorporation were measured. An early expression of CD69, but not of CD25, antigen was detectable after 24-72 h of stimulation on up to 80% of natural killer (NK) cells and up to 10% of CD4+ T cells in PBMC cultures. Anti-IL-2 antibodies inhibited these increases of CD69 on NK cells and T cells by up to 60%. After 6 days of antigenic stimulation, the rates of both CD25+ and CD69+ lymphocytes were higher. Seventy-four percent of the CD25+ PBMC but only 55% of the CD69+ cells were CD3+ T lymphocytes at this time. No qualitative differences were detectable in allergen- or tetanus-toxoid-stimulated PBMC from allergic patients. The high expression of CD69 on NK cells in antigen-stimulated cultures suggests that these cells are easily activated by cytokines from antigen-stimulated T cells. CD69+ NK cells may serve as early-indicator cells in cultures with antigen- or allergen-stimulated mononuclear cells.

Adult↗
PubMed2002

Multiple cis-acting elements regulate the expression of the early T cell activation antigen CD69.

CD69 is the earliest activation antigen expressed on T lymphocytes upon stimulation through the TCR, or with stimuli that mimic TCR triggering. Here we describe that the phorbol ester PMA and a calcium ionophore had a synergistic effect on both CD69 antigen expression and promoter activity in Jurkat cells, that was sensitive to cyclosporin A (CsA). CD69 promoter analysis indicated that the sequence -78 to +16 contained the elements responsible for PMA and PMA plus calcium ionophore induction, as well as CsA inhibition. Mutagenesis of two previously described AP-1 motifs did not affect either the basal or the inducible promoter activities. Electrophoretic mobility shift assays allowed the identification of three novel inducible complexes composed by Egr-1/Egr-3, Egr-1, and ATF-3/Fos. Mutation of each sequence resulted in a partial reduction of the basal promoter activity, whereas the inducibility by PMA plus calcium ionophore remained almost unaffected. It was necessary to combine at least two mutations to obtain a significative or complete reduction of the response to the mitogenic stimulus. These results indicate that the inducible expression of CD69 gene by mitogenic signals is regulated by multiple cis-acting elements and by the interplay of transcription factors of the AP-1, EGR and ATF/CREB families.

Activating Transcription Factor 3↗
PubMed1999

Induction of surface antigen CD69 expression in T-lymphocytes following exposure to actinomycin D.

The expression of surface antigen CD69 in immune response cells is typically associated with the early stage(s) of cell activation, with maximal expression levels within 4 h of appropriate antigenic or mitogenic stimulation, and maintenance of these high expression levels for 18-24 h. The expression profiles of CD69 in human peripheral blood mononuclear cells (PBMC) cultured with actinomycin D prior to mitogenic stimulation were evaluated by direct immunofluorescence using flow cytometry. Pretreatment of PBMC suspensions with low, non-toxic levels of actinomycin D stimulated CD3+ T-lymphocytes to express CD69 in a concentration-dependent manner. Furthermore, CD4+ T-lymphocytes were the primary cells responding in this fashion. Secondary mitogenic stimulation following antibiotic treatment potentiated cellular CD69 expression in these assays. CD69 expression was profoundly suppressed with in vitro actinomycin D concentrations >/=1-2 microg/ml, presumably by interference with cellular transcription/translation mechanisms. Parallel thymidine incorporation assays indicated that actinomycin D effectively inhibited thymidine uptake in a concentration-dependent manner, with complete inhibition at >/=0.1 microg/ml. The evaluation of cell cycling dynamics following antibiotic treatment, with and without secondary mitogen stimulation, indicated no substantial changes in DNA synthesis over controls. The diversity of these responses suggests that expression of CD69 may not solely reflect mitogenic activation status but may, under some conditions, result from induced cellular stress.

Antigens, CD↗
PubMed1992

Expression of activation antigens CD69, HLA-DR, interleukin-2 receptor-alpha (IL-2R alpha) and IL-2R beta on T cells of human decidua at an early stage of pregnancy.

T cells of human decidua at an early stage of pregnancy were examined by flow cytometry for the expression of the T-cell-activation antigens CD69, HLA-DR, interleukin-2 receptor-alpha (IL-2R alpha) and IL-2R beta. The decidua contained a small number of T cells and both CD4+ and CD8+ subsets expressed CD69, HLA-DR, IL-2R alpha and IL-2R beta antigens significantly whereas, in peripheral blood, only a small number of T cells expressed these activation antigens. These findings indicate that T cells in the decidua in the first trimester of pregnancy are regionally activated.

Antigens, CD↗
PubMed1998

Participation of the CD69 antigen in the T-cell activation process of patients with systemic lupus erythematosus.

Accumulating evidence has implicated T cells in the pathogenesis of systemic lupus erythematosus (SLE). The CD69 antigen is an integral membrane protein rapidly induced on the surface of activated lymphocytes. We obtained CD4+ and CD8+ T cells from normal subjects and patients with SLE. The percentage of CD69 expression in freshly isolated cells and after in-vitro incubation with mitogens was quantified by three-colour immunofluorescent staining. Expression of this protein was increased in both CD4+ and CD8+ T-cell subsets from SLE patients when compared with normal cells, although the difference was significant only in the CD8+ T-cell subset (P = 0.05). Cellular activation increased CD69 expression. When stimulated with anti-CD2/CD2R or phytohaemagglutinin (PHA), the percentage and absolute numbers of CD69+ cells were lower in patients than in controls. Addition of anti-interleukin (IL)-10 monoclonal antibody (MoAb) increased the percentage of in-vitro CD69 expression in SLE cells. These results suggest that the peripheral blood lymphocytes from patients with SLE have an intrinsic defect that alters their activation process, including the expression of CD69, and might explain some of the T immunoregulatory abnormalities observed in these patients.

Adolescent↗
PubMed2000

Induction of the activation-related antigen CD69 on human eosinophils by type IIA phospholipase A2.

OBJECTIVE: High levels of human type IIA phospholipase A2 (PLA2-IIA) have been found in the eosinophil-mediated inflammation sites, although the pathophysiological role of PLA2-IIA in the eosinophil activation has remained poorly understood. We investigated the effects of PLA2-IIA on eosinophil activation. METHODS: Eosinophils were incubated with recombinant human PLA2-IIA or other stimuli, and then eosinophil peroxidase (EPO) (by colorimetric assay) and leukotriene C4 (by enzyme immunoassay) released in the incubation buffer were measured. Expression of CD11b and CD69 on the cell surface was also measured by flow cytometry (by mean fluorescence intensity (MFI)). EPO, LTC4, and CD11b are thought to be markers for early phase activation (occurred in an hour after stimulation), and CD69 is to be a marker for late phase activation (occurred after several hours). RESULTS: While PLA2-IIA (5 microg/ml) did not induce any early phase activation, it induced significant expression of an activation-related antigen, CD69, on human blood eosinophils. The PLA2-IIA, when enzymatically inactivated by either p-bromophenacyl bromide or EDTA, lost its effect on the CD69 induction. Similarly to PLA2-IIA, several lysophospholipids (1 microg/ml) also induced CD69 on eosinophils significantly (control, 0.71 +/- 0.11; PLA2-IIA, 3.29 +/- 0.37*; lysophosphatidic acid, 2.57 +/- 0.43*; specific MFI +/- S.E.M., n = 4, * indicate p < 0.05 vs. control). CONCLUSIONS: PLA2-IIA induces CD69 expression on the eosinophils through its catalytic activity at least partly via the enzymatic products such as several lysophospholipids from the eosinophil membrane phospholipids. PLA2-IIA may contribute to the eosinophilic inflammation synergistically with other factors.

Antigens, CD↗
PubMed1998

Expression of the activation antigen CD69 predicts functionality of in vitro expanded peripheral blood mononuclear cells (PBMC) from healthy donors and HIV-infected patients.

Gene therapy for AIDS necessitates harvest and expansion of PBMC from HIV-infected patients. We expanded PBMC from healthy blood donors and HIV-infected patients for up to 14 days using four expansion protocols: 3 days of phytohaemagglutinin (PHA) stimulation, continuous PHA stimulation, 3 days of stimulation with anti-CD3 and anti-CD28, and continuous stimulation with anti-CD3 and anti-CD28. Functionality of PBMC was evaluated prior to and after expansion using standard proliferation assay. Phenotype and lymphocyte subset activation defined by expression of CD69 and CD25 were determined using flow cytometry. PBMC from healthy donors and HIV-infected patients were readily expanded. The best expansion was obtained using stimulation for 3 days. After expansion, functionality of PBMC measured as proliferative response was partly conserved. PBMC expanded with stimulation for 3 days exhibited more preserved functionality than PBMC stimulated continuously (P < 0.03). The mean proliferative response in each of the four different expansion protocols correlated with the mean values of CD69 expression. The proliferative responses from patients and healthy donors expanded with PHA stimulation for 3 days correlated with CD69 expression on CD4 cells (r = 0.68, P < 0.01) and on CD8 cells (r = 0.59, P < 0.03). Furthermore, expression of CD69 reliably predicted which patients and donors had highly conserved functionality after in vitro expansion. Finally, PBMC expanded with PHA stimulation for 3 days were examined for apoptosis. Only a minor fraction was primed for apoptosis, and this fraction could be significantly reduced by addition of IL-2 to the culture medium (P < 0.05). In conclusion, the feasibility of expanding PBMC from HIV patients was demonstrated. Expanded PBMC had conserved functionality. Finally, after in vitro expansion, expression of the activation antigen CD69 reliably predicted functionality of PBMC.

Adult↗
PubMed1994

The activation antigen CD69.

One of the earliest cell surface antigens expressed by T cells following activation is CD69, which is detectable within one h of ligation of the T cell receptor/CD3 complex. Once expressed, CD69 acts as a costimulatory molecule for T cell activation and proliferation. In addition to mature T cells, CD69 is inducibly expressed by immature thymocytes, B cells, natural killer (NK) cells, monocytes, neutrophils and eosinophils, and is constitutively expressed by mature thymocytes and platelets. Recently, cDNA clones encoding human and mouse CD69 were isolated and showed CD69 to be a member of the C-type lectin superfamily. Gene mapping studies have placed CD69 on distal mouse chromosome 6 and human chromosome 12p13, close to, if not in, the NK gene complex. The structure, chromosomal localization, expression and function of CD69 suggest that it is likely a pleiotropic immune regulator, potentially important not only in NK cell function but also in the activation and differentiation of a wide variety of hematopoietic cells.

Animals↗