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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human T lymphocyte proliferative response induced via CD28 molecule is analyzed. An anti CD28 MoAb, CLB-CD28/1, induces the proliferation of human peripheral blood mononuclear cells in the absence of other stimuli, indicating that CD28 molecule can directly mediate a mitogenic signal in this system. The mitogenic activity of MoAb CLB-CD28/1 on PBMC does not require MoAb interaction with monocyte Fc receptors, since F(ab')2 fragments from the MoAb are mitogenic to the same extent as whole IgG. Nevertheless, the activity depends on the presence of accessory cells, since purified T lymphocytes require addition of irradiated monocytes and interleukin 2 to proliferate when incubated with MoAb CLB-CD28/1. On the other hand, MoAb CLB-CD28/1 induces response to IL-2 in thymocytes in the absence of accessory cells. Cooperation of MoAb CLB-CD28/1 with three other MoAbs, recognizing CD3, CD5 and HLA Class I antigens, respectively, induces Tac antigen expression and IL-2 responsiveness in purified T lymphocytes. This effect is obtained without cross-linking of the MoAb. It does not rely on a physical association between CD28 and CD3, CD5 or HLA Class I molecules, as demonstrated by co-modulation experiments. These data indicate that expression of IL-2 receptor on T lymphocytes can result from interaction of multiple activation pathways and that some of them, such as those mediated by CD5 and HLA Class I antigens, previously reported to serve as modulatory circuits, can instead act as essential elements in the onset of T lymphocyte proliferation.
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PMID:Mitogenic activity of anti-CD28 MoAb CLB-CD28/1 on peripheral blood mononuclear cells and its cooperation with other anti-T cells MoAb in the activation of purified T lymphocytes. 170 Oct 62

A number of markers which have been proposed to identify B cell subsets have been reassessed on human B cells, using an immunofluorescence technique optimized for sensitivity and an analytical mode which yields histograms showing the distribution of fluorescence on B cells. The results show that CD38, CD22, CD23, FMC6, and anti-IgM react with all blood B cells, albeit with a broad and complex distribution of fluorescence. CD5, CD9, CD10, CD43, and IgD can be regarded as subset markers since they give clearly bimodal distributions of fluorescence intensity. CD5 staining showed at least three populations, with a small number (3-5 per cent) of cells brightly stained and a population of variable size staining weakly. No clearly defined populations were seen with CD45R0, although staining was slightly above background. An antibody against the LAM-1 molecule reacted with all blood B cells. Expression of the IL-2 receptor p55 chain (CD25) was clearly bimodal, whereas the p75 chain was essentially negative on B cells. The relationship between subsets in blood and subsets in tissue, and between subsets identified by different markers in blood, is discussed.
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PMID:The expression of sub-population markers on B cells: a re-evaluation using high-sensitivity fluorescence flow cytometry. 172 68

The majority of non-Hodgkin's lymphomas (NHLs) are of B-cell lineage, with less than 20% of cases being of T-cell lineage. The B-cell NHLs phenotypically correspond to normal cells in the mid stages of normal differentiation. More specifically, by their expression of B-cell activation antigens, these tumors are the neoplastic counterparts of normal activated B cells. The follicular lymphomas--including the small cleaved, mixed small and large cell, and large cell types, as well as the small noncleaved cell (Burkitt's) lymphomas--represent malignant expansions of normal germinal center B cells by their expression of pan-B cell antigens, B-cell activation antigens, and CD10 (CALLA). The diffuse lymphomas also correspond to normal activated B cells. The small lymphocytic lymphomas express the low-affinity IL-2 receptor and CD5, both of which are induced on normal B cells following mitogen stimulation. The other diffuse B-cell NHLs similarly express activation antigens and resemble "transformed" B cells. The T-cell NHLs generally correspond to normal activated CD4+ T cells. These tumors--which include most peripheral T-cell lymphomas, cutaneous T-cell lymphomas, and HTLV-I-associated adult T-cell leukemias/lymphomas--express antigens induced on activated T cells, including IL-2 and transferrin receptors (CD25 and CD71, respectively), as well as HLA-DR. The lymphoblastic lymphomas, which are generally of T-cell lineage, phenotypically correspond to stages of intrathymic differentiation, often by their coexpression of CD4 and CD8, as well as expression of CD1. It remains controversial whether the immunophenotype of lymphoblastic lymphoma differs significantly from T-cell acute lymphoblastic leukemia. Since immunologic heterogeneity of NHL was first observed, attempts have been made to employ the data as a prognostic variable. Early studies suggested that lineage derivation or expression of markers of proliferating cells affected outcome in NHL. However, these reports were often retrospective, included various histologies, and did not treat patients uniformly. More recent prospective studies with relatively uniformly treated patients, predominantly involving DLCL, suggest that certain immunologically defined subgroups may have significantly different clinical outcomes. However, additional clinical studies will be necessary before treatment options are based upon immunologic markers.
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PMID:Immunologic markers in non-Hodgkin's lymphoma. 193 59

Transmembrane signaling of normal human T cells was explored with mAbs directed at TCR, CD2, CD4, CD5, or CD8 antigens and highly purified CD4+ T cells and CD8+ T cells. Our experiments explicitly show that: (a) crosslinkage of TCR with the CD2 antigen, and not independent crosslinking of TCR and of CD2 antigen or crosslinking of either protein with the CD4 or CD8 antigen induces significant proliferation independent of co-stimulatory signals (e.g., accessory cells, recombinant lymphokines, or tumor promoter), (b) F(ab')2 fragments of mAb directed at the TCR and F(ab')2 anti-CD2, crosslinked with F(ab')2 fragments of rabbit anti-mouse IgG, promote the proliferation of highly purified T cells, (c) a prompt and sustained increase in intracellular free Ca2+ concentration results from crosslinkage of TCR with the CD2 antigen, (d) T cell proliferation induced by this novel approach is curtailed by EGTA and by direct or competitive inhibitors of PKC, (e) crosslinkage of TCR with the CD2 antigen results in the transcriptional activation and translation of the gene for IL-2 and in the expression of IL-2 receptor alpha (CD25), (f) anti-CD25 mAbs inhibit T cell proliferation initiated by crosslinkage of TCR with the CD2 antigen, and recombinant IL-2 restores the proliferative response. Our first demonstration that crosslinkage of TCR with the CD2 antigen induces proliferation of normal human CD4+ T cells and CD8+ T cells, in addition to revealing a novel activation mechanism utilizable by the two major subsets of T cells, suggest that the CD2 antigen might be targeted for the regulation of antigen-specific T cell immunity (e.g., organ transplantation).
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PMID:A novel model for antigen-dependent activation of normal human T cells. Transmembrane signaling by crosslinkage of the CD3/T cell receptor-alpha/beta complex with the cluster determinant 2 antigen. 197 76

The effects of microgravity on the immune system are largely unknown, but understanding such effects becomes increasingly important as space exploration continues and mission duration increases. Reductions in postflight human T cell reactivity to mitogens is well documented. Similar results have been obtained using a clinostat as an in vitro model of microgravity. In this study, a rat tail suspension model of weightlessness was used to examine in vitro lymphocyte proliferation in response to mitogens. Experiments were designed to uncover potential deficits in events related to proliferation including cell surface protein and IL-2 receptor (IL-2R) expression, interleukin-2 (IL-2) production, and accessory cells. Suspension of rats for 1 week led to a significant depression in [3H]thymidine incorporation by mitogen-stimulated peripheral blood lymphocytes (PBL) but only a small decrease in the proliferation of lymph node lymphocytes and splenocytes. There were no changes in the percentages of cells expressing CD4, CD5, CD8 or immunoglobulin. Moreover, no changes in IL-2 production or IL-2R expression were observed. More esterase-positive macrophages were detected in all lymphatic tissues of suspended rats, but there was no corresponding increase in the percentage of cells bearing the macrophage markers OX41 or OX42. This increase in the number of macrophages may be related to the observed suppression of lymphocyte proliferation. The tissue specificity of the decrease in mitogen activation indicates that there may be a compartmentalized response in the rats tested in the hindlimb suspension model.
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PMID:Effect of hindlimb suspension simulation of microgravity on in vitro immunological responses. 207 Aug 18

The majority of CLLs are of B lineage derivation with about 5 per cent of cases of T lineage. Although morphologically resembling the small peripheral blood B cell, by virtue of the expression of B cell restricted and associated cell surface antigens, B-CLLs are not the neoplastic counterparts of normal resting B cells. Similar to the peripheral blood B cell, B-CLLs express CD19, CD20, CD21, CD24, CD40, CD44, CD45R, and sIgM/D. However, unlike peripheral blood B cells, B-CLLs generally do not express C3b complement receptor, LFA-1, or CD22. In addition, B-CLLs express the T cell associated antigen CD5, and a number of antigens induced on normal B cells following in vitro activation (B5, Blast-1, CD23). These findings support the hypothesis that B-CLLs are the neoplastic counterparts of one or more unique subpopulations of normal B cells. Normal CD5+ B cells, which phenotypically resemble B-CLL, are present in fetal lymphoid tissues and in small numbers in adults. Moreover, normal CD5+ B cells are present in increased numbers in patients with autoimmune diseases and a subset of normal in vitro activated B cells phenotypically resemble B-CLL. Similar studies into the state of differentiation of T-CLL cells suggest that although most cases resemble normal activated T helper cells, a significant number are the neoplastic counterparts of natural killer cells. Recent studies have examined the function of B and T cells in B-CLL. Although controversial, these studies suggest that the in vitro response to mitogens and cytokines of B-CLL cells is abnormal. T cell proliferation in B-CLL is depressed due to an inability to produce sufficient T cell growth factor (IL-2) as well as a poor response to exogenous IL-2 possibly from ineffective IL-2 receptor expression. Purified populations of T helper and T suppressor cells demonstrate insufficient support of Ig production by normal B cells as well as excess suppression, respectively. These studies have further supported the previous hypothesis that the depressed cellular and humoral immunity in CLL is multifactorial with both abnormal B and T cell function.
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PMID:Immunobiology of chronic lymphocytic leukemia. 218 99

Human B lymphocytes undergo distinct phenotypic changes following activation with antigen and polyclonal mitogens. Increasing interest has focused on the unique subpopulation of B cells that expresses the CD5 antigen. In this study, we examined the signals that induce the expression of CD5 on normal splenic B cells. Only 12-O-tetradecanoylphorbol-13-acetate (TPA) induced CD5 expression on highly purified splenic B cells, whereas anti-immunoglobulin (anti-Ig), Epstein-Barr virus, anti-CD20, recombinant interleukin-1 (rIL-1), rIL-2, rIL-4, recombinant interferon-gamma (rINF-gamma), and B-cell growth factor all failed to induce CD5 expression. The expression of CD5 was detected on the cell surface by 48 hours and decreased by 96 hours. Dual-fluorochrome analysis demonstrated that the CD5+ B cells coexpressed the B-cell activation antigens B5, IL-2 receptor, and CD23, thereby providing phenotypic evidence that this B-cell subpopulation is activated. In vitro studies of dual-fluorochrome-sorted, TPA-stimulated splenic B cells demonstrated significantly greater tritiated thymidine incorporation and Ig secretion by the CD20+ CD5- cells than by the CD20+ CD5+ subset. These phenotypic and functional studies are consistent with the notion that TPA-induced CD5+ B cells are a subset of in vitro activated B lymphocytes.
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PMID:Studies of in vitro activated CD5+ B cells. 246 35

CD28 is an antigen of 44 kDa which is expressed on the membrane of the majority of human T cells. The present study examines the functional effects of an anti-CD28 monoclonal antibody (mAb 9.3) on T cell activation induced with immobilized anti-CD3 mAb OKT3 or with mitogens, in the absence of accessory cells. To this end, we used blood resting T cells that were completely depleted of accessory cells (monocytes, B cells, and natural killer cells), and consequently did not respond to recombinant interleukin-2 (rIL-2), to immobilized OKT3, to PHA, or to Con A. Addition of mAb 9.3 to the cultures enhanced IL-2 receptor expression (Tac antigen) on PHA- or immobilized OKT3-stimulated T cells and induced IL-2 receptors on Con A-stimulated T cells. Moreover, addition of mAb 9.3 to cultures of T cells stimulated with PHA, Con A, or immobilized OKT3 resulted in IL-2 production. Soluble mAb 9.3 was a sufficient helper signal for T cell proliferation in response to PHA or immobilized OKT3. Crosslinking of mAb 9.3 by culture on anti-mouse IgG-coated plates enhanced the helper effect and was an essential requirement for the induction of T cell proliferation in response to Con A. No other anti-T cell mAb (anti-CD2, -CD4, -CD5, -CD7, -CD8) was found to provide a complete accessory signal for PHA or Con A stimulation of purified T cells. T cell proliferation induced by the combination of PHA and mAb 9.3 was strongly inhibited by the anti-IL-2 receptor mAb anti-Tac. In conclusion, mAb 9.3 can provide a signal bypassing monocyte requirement in T cell activation with immobilized OKT3, PHA, and Con A, resulting in an autocrine IL-2-dependent pathway of proliferation.
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PMID:The anti-T cell monoclonal antibody 9.3 (anti-CD28) provides a helper signal and bypasses the need for accessory cells in T cell activation with immobilized anti-CD3 and mitogens. 253 66

Several monoclonal antibodies directed against a number of T cell surface molecules are used to elucidate the role of these molecules (cell surface molecules) in T cell activation. The activation of T cells via these molecules are both antigen-dependent (CD3/TcR complex) and antigen-independent. Irrespective of their antigen dependency, these monoclonal antibodies activate T cells by a classical signal transduction pathway, in which the binding of monoclonal antibodies to their cell surface receptors leads to activation of phospholipase C resulting in the depolarization of plasma membrane, hydrolysis of IP2 and IP3 and DAG, the 'second messengers'. IP3 leads to mobilization of intracellular calcium to contribute to an increase in [Ca++]i, whereas DAG causes activation and translocation of PKC and an increasing apparent affinity for Ca++. The role of IP4 in the mobilization of intracellular calcium is emerging. In addition, influx of extracellular calcium also contributes to increase in [Ca++]i. The increase in [Ca++]i following activation via some T cell surface antigen is predominantly due to intracellular mobilization of Ca++ (e.g. CD3/TcR complex), whereas activation via other T cell surface antigen, the increase in [Ca++]i is almost entirely due to an influx of extracellular calcium (e.g. CD5 antigen). All these molecules activate autocrine system of T cell growth, namely IL-2 production, IL-2 receptor expression and T cell proliferation.
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PMID:Mechanisms of transmembrane signalling in human T cell activation. 269 33

The expression of human cell-membrane antigens by hybrid cell lines derived by fusing a human B-ALL and mouse BW 5147 T-lymphoma cells has been studied. Using monoclonal antibodies (mAb), the phenotypes of 19 of the 24 hybrids which grew 11-44 days post-fusion have been analysed by indirect membrane immunofluorescence (IF). These uncloned hybrid cells were assayed early after outgrowth, prior to extensive human chromosome and antigen loss. Nonetheless, cytogenetic analysis showed that all hybrids contained variable numbers of human chromosomes. Phenotypic analysis showed that the hybrids could be grouped as follows: a high frequency expressing CD25 (IL-2 receptor), human T200, HLA class I alpha and beta 2microglobulin, and reacting with the mAb H207 and 12E7; an intermediate frequency expressing CD1 and CD2; and a low frequency expressing CD3, CD4, CD5, CD7, CD8 and CD9. This pattern of antigen expression resembled the frequency of these cells in the human B-ALL parent line. Cell sorting was used to immunoselect hybrids expressing CD1 and CD2, but CD1 expression was unstable during subsequent culture.
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PMID:Expression of human CD antigens, including CD1 and CD25, by human x mouse interlineage leukaemia hybrids. 342 25


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