Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effective stimulation of CD4+ T cells in an immune response depends on activation signals transduced via not only the CD3-T-cell receptor (TCR) complex but also those generated by accessory cell-surface proteins, including some that mediate adhesion between T cells and antigen-presenting cells (APC). Three members of the Ig superfamily, CD54 [intercellular cell adhesion molecule 1 (ICAM-1)], CD58 [lymphocyte function-associated antigen 3 (LFA-3)], and B7, expressed on the surface of APC, have been shown to mediate both adhesion and signaling during T cell-APC interactions. Recently another member of the Ig superfamily, [vascular cell adhesion molecule 1 (VCAM-1; INCAM110)], has been identified. VCAM-1 mediates adhesion between endothelial cells and activated lymphocytes and certain tumor cells. Here, using a soluble VCAM-1 fusion protein with receptor globulin (Rg), we examined the role of VCAM-1 in T-cell activation. We observed that CD4+ T cells, which are inefficiently stimulated by immobilized anti-TCR-1 or anti-CD3 monoclonal antibody (mAb) alone, can be induced to proliferate when exposed to immobilized VCAM-1-Rg in conjunction with either immobilized anti-TCR-1 or immobilized anti-CD3 mAb. The costimulatory effects of VCAM-1-Rg on CD4+T cells is inhibited by mAb to either the CD29 (integrin beta 1)-CD49d [very late activation antigen 4 alpha (VLA-4 alpha)] complex on the surface of CD4+ T cells or to VCAM-1. Stimulation of CD4+ T cells with immobilized VCAM-1-Rg and anti-TCR or -CD3 mAb results in the synthesis of both interleukin 2 (IL-2) receptors and IL-2. In addition, anti-CD25 (anti-IL-2 receptor a) mAb significantly inhibited the VCAM-1-Rg/anti-TCR or -CD3 mAb-driven activation of CD4+ T cells, indicating that endogenously produced IL-2 is in part responsible for the observed T-cell proliferation. Collectively, these results suggest that VCAM-1 can play an important costimulatory role during the activation of CD4+ T cells.
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PMID:Vascular cell adhesion molecule 1 induces T-cell antigen receptor-dependent activation of CD4+T lymphocytes. 171 78

This manuscript reviews recent studies on the characterization of functional surface antigens on human NK cells. A series of cloned NK cell lines has been utilized for examination of these structures. These clones provide a relatively large number of cells with a stable phenotype and consistent specific cytotoxicity, which reflect the diversity of uncultured NK cells in normal peripheral blood. Almost all clones express the T11 antigen, some have a mature T-cell phenotype (T3+, T11+), and only one (JT1) does not reveal any T-cell antigen at all (T3-, T11+). Using NK clones to generate monoclonal antibodies specific for NK-associated antigens, two structures have been identified, NKH1 and NKH2. NKH1 appears to be exclusively expressed on large granular lymphocytes (LGL) of peripheral blood and was found to be a pan-NK cell antigen. NKH2 is also expressed primarily by LGL, but NKH2-positive LGL do not display a high level of NK activity. Another surface structure that has been found to play an important role in NK cell function is the T11 antigen/E rosette receptor complex, which is expressed in 80% of peripheral blood NK cells. The T11 antigen complex has been described as possessing the T11(1), T11(2), and T11(3) antigens and is an important alternate pathway for antigen-independent T-cell activation. Using anti-T11(2) and anti-T11(3) monoclonal antibodies, IL-2 receptor expression could be induced on various NK clones if they expressed the correct T11 antigenic epitope. As anti-T11 2/3 antibodies had a direct proliferative effect on NK cells with mature T-cell phenotype (T3+), it is proposed that the production of IL-2 by NK clones is largely dependent on the T-cell phenotype of NK cells. All NK clones expressed IL-2 receptor at low density and therefore needed a ten fold higher concentration for maximal proliferation than T-cell clones. For some T-cell-like NK clones, the T3 antigen complex and a T-cell receptor-like structure, NKTa or NKTb, have been shown to define the target cell specificity. The activation antigen, TNKTAR, was characterized as the recognition structure on the target cell for these NK cells. For both T3- and T3+ NK clones, the LFA-1 antigen has been shown to play an important role in effector/target cell interaction. As previously described for CTL, the LFA-1 molecule is involved in NK cytotoxicity as a nonspecific adhesion-strengthening molecule at the effector cell level.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Functional surface structures on human natural killer cells. 241 57

Effects of anti-IL2 receptor antibody (anti-IL2 RAb) and cyclosporin A (CsA) on human T cell proliferation in primary mixed lymphocyte reaction (MLR) were investigated. Both agents inhibited the proliferative response induced by alloantigen in a dose dependent manner when they were added at the initiation of culture. We also analyzed the expression of activation antigen on responder cells and the kinetics of T lymphocyte subset proliferation during MLR using two-color flow cytometry. Cells expressing activation antigens, such as IL-2 receptor and HLA-DR, were found less frequently in anti-IL2 RAb-treated MLR culture (4.8%) than in CsA-treated MLR culture (16.5%) on day 6. Furthermore, proliferation of CD8+CD11- cells, considered a cytotoxic T cell subset, were inhibited significantly more in anti-IL2 RAb-treated MLR culture than in CsA-treated MLR culture. We further demonstrate that CsA inhibits preferentially IL-2 production and anti-IL2 RAb inhibits T cell proliferation by blocking an absorption of IL-2 by activated lymphocytes. These data suggest that anti-IL2 RAb selectively inhibits alloantigen-activated T cells and may prove to be of significant value as an immunosuppressive agent in clinical organ transplantation.
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PMID:Effects of anti-interleukin-2 receptor antibody and cyclosporin A on human T cell proliferation in primary mixed lymphocyte reaction. 252 99

To examine the relationship between lymphocyte phenotypes and states of activation in patients with Bancroftian filariasis, dual colour flow cytometry and concurrent in vitro cell culture were performed on normal individuals (NV; n = 15), and on patients with either asymptomatic microfilaraemia (MF; n = 12) or elephantiasis (CP; n = 11). In contrast to findings by others in a population with Brugian filariasis, the percentages of total B lymphocytes (CD19), T lymphocytes (CD3), helper/inducer T lymphocytes (CD4), and suppressor/cytotoxic T lymphocytes (CD8) in both patient groups were found to be within the range defined by clinically normal individuals. Furthermore, there were no differences among the groups in the expression of the IL-2 receptor (CD25) on T cells. There was, however, a significantly greater proportion (P less than 0.01) of 'activated' cytotoxic/suppressor lymphocytes (defined by co-expression of CD8 and HLA-DR) in patients with elephantiasis (16.4 +/- 8.6%) than in the MF (8.9 +/- 2.6%) or NV (8.3 +/- 2.9%) groups. Further, when the expression of this activation antigen was examined in parallel with in vitro mitogen responsiveness, an inverse correlation between the percentage of CD8+ HLA-DR+ lymphocytes and pokeweed mitogen-induced proliferation was seen (r = -0.54; P less than 0.001). These data provide further definition of the immunoregulatory abnormalities seen in human filarial infections and suggest that activated CD8+ T lymphocytes may be involved in the pathogenesis of the chronic obstructed lymphatic form of this disease.
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PMID:Lymphocyte subpopulations in Bancroftian filariasis: activated (DR+) CD8+ T cells in patients with chronic lymphatic obstruction. 252 54

The characteristics of a novel T lineage-specific activation antigen, termed TLiSA1, are described. The antigen was detected with a mouse monoclonal antibody, LeoA1, that was raised against activated human T cells generated in mixed lymphocyte culture (MLC). The antigen became strongly expressed on T cells 48-72 h after stimulation with phytohemagglutinin, and retained expression on MLC-activated T cells after 10 d of culture. The antigen was absent from a range of human T, B, myeloid, fibroblast, and tumour cell lines, but was present on the surface of the interleukin 2 (IL-2)-dependent gibbon cell line MLA-144. Analysis of the antigen by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of immunoprecipitates obtained from activated human T cells demonstrated a broad band in the region of 70 kD, whereas precipitates obtained from MLA-144 revealed a single narrow band of 95 kD. The molecule was expressed with a maximum density of 66,000 copies per cell on the surface of MLC-activated T cell blasts, as assessed by Scatchard analysis. TLiSA1 was distinguished from the IL-2 receptor bound by the anti-Tac monoclonal antibody by demonstrating that the antigens did not comodulate or coprecipitate, and by constructing an IL-2-independent human T X T hybrid that expressed the TLiSA1 but not the Tac antigen. MLC with B lymphoblasts was used to generate cytotoxic T lymphocytes (CTL) specific for the stimulating cell, and anomalous killer (AK) cells able to kill melanoma target cells. The presence of LeoA1 or F(ab')2 fragments of the antibody from the beginning of coculture did not affect proliferation in these cultures, but did inhibit the induction of both CTL and AK cells from their precursors. This inhibition of differentiation by LeoA1 was confirmed under conditions of limiting dilution, where it was shown that the antibody reduced the frequency of CTL produced, and greatly (fourfold) reduced the frequency of AK cells generated from their precursors. We discuss the possibility that human CTL may express a differentiation factor receptor that is distinct from the receptor for IL-2.
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PMID:TLiSA1, a human T lineage-specific activation antigen involved in the differentiation of cytotoxic T lymphocytes and anomalous killer cells from their precursors. 258 Sep 33

This study was undertaken to explain the molecular basis for the diverse pathology and clinical behavior of postthymic T cell malignancies. Total cellular RNAs were extracted from four HTLV-1 positive and ten HTLV-1-negative T cell lymphomas and cell lines, and investigated for homology with cloned DNA probes specific for interleukin-2 (IL-2), IL-2 receptor (IL-2R), transforming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF), and epidermal growth factor receptor (EGF-R). Tumor cells associated with clinically high grade HTLV-1-positive adult T cell leukemia (ATL) and large cell morphology (T immunoblastic lymphomas) were found to have higher levels of expression of IL-2 and TGF-beta genes than low grade T cell neoplasms (mycosis fungoides and Sezary's syndrome). High expression of IL-2R gene was restricted to Ki-1-positive lymphomas and to one ATL. Cell lines corresponding to the advanced stage of a cutaneous T cell lymphoma (CTCL) showed enhanced expression of PDGF. Therefore, high grade T cell malignancies had consistently elevated expression of growth factor/receptor (GF/R) genes. Expression of EGF-R was negligible in all T cell malignancies. An inverse relationship was found between the expression of T cell antigen receptor (differentiation antigen) and GF/R (activation antigen) genes, accounting for the frequent aberrant expression of T cell antigens in high grade T cell lymphomas. The results suggest that post-thymic T cell malignancies derived from activated T cells produce and secrete GF, conferring a growth advantage on neoplastic T cells, and correlating well with their histologic subtype and clinical behavior.
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PMID:Expression of growth factor/receptor genes in postthymic T cell malignancies. 278 74

Twenty-two patients with adult onset aplastic anaemia were analysed before and after therapy with anti-thymocyte globulin (ATG). Lymphocyte phenotype, lymphokine levels or production, and haematopoietic progenitor cell number were measured 3 months after therapy; clinical response was determined 1 year post-therapy. By flow cytometry there was a significant reduction in both the proportion and absolute number of peripheral blood lymphocytes expressing activation antigen Tac (IL-2 receptor) and in the proportion of HLA-DR+ lymphocytes. For T cells bearing HLA-DR, there were proportional decreases in both activated helper and suppressor cells. There was no statistically significant difference pre-ATG to post-ATG in the absolute numbers of total, helper and suppressor lymphocytes. In all 10 haematologic responders the number of Tac bearing lymphocytes after ATG therapy was in the normal range, but half of 12 non-responding patients continued to have abnormally elevated numbers of Tac+ T cells. The proportion of Tac+ cells were not related to transfusion history. Gamma-interferon levels in serum by radioimmunoassay were elevated in almost half the aplastic patients; post-ATG, gamma-interferon was detectable in only three patients. Haematologic response to ATG therapy was associated with increased numbers of haematopoietic progenitors post-treatment, but pre-treatment values were not predictive of a response. These results are consistent with a pathogenic role for activated T-cells and their lymphokine products and suggest that the target of ATG therapy may be a Tac+ lymphocyte.
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PMID:Lymphocyte phenotype and lymphokines following anti-thymocyte globulin therapy in patients with aplastic anaemia. 311 88

This study describes VG01, a monoclonal antibody to a novel lymphocyte activation antigen. The cells reacting with VG01 were first characterized by indirect immunofluorescence and fluorescence-activated cell sorter analysis. The antigen defined by VG01 was expressed on circulating T lymphocytes (23.8 +/- 9.0) and on the majority of large granular lymphocytes and monocytes (greater than 90%), while granulocytes stained weakly. All other cells tested so far--thymocytes, hematological malignancies and several cell lines--were negative. Upon activation with mitogens or allogeneic cells more than 90% of the transformed lymphocytes became VG01-positive. The kinetic studies demonstrated that the antigen defined by VG01 lags the expression of the IL-2 receptor by 48 hr and remains present for up to 18 days after stimulation in culture. Thus, this antigen does not seem to be involved in the initial steps of T cell activation and its expression continues after cell division has stopped. Assays with purified sorted populations showed that lymphocyte proliferation to mitogens and in mixed lymphocyte culture came primarily from the VG01- population. The responding cells became VG01+ during activation--and when alloantigen-primed lymphocytes were sorted and restimulated with the original stimulators, all the in vitro memory response came from the VG01+ population. Thus, VG01 antibody is efficient in selecting for alloreactive T lymphocytes in vitro and has potential for selective modulation of immune responses. Its reactivity with activated T cells and NK cells may also help define a common functional program for these two cell types, adding to the understanding of their mechanism of action and/or their origin.
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PMID:A novel lymphocyte activation antigen present on allospecific primed lymphocytes and defined by the monoclonal antibody VG01. 313 Jul

The relevant anti-tumour mechanisms of recombinant interleukin-2 (rIL-2) in vivo are unclear but an influx of T-lymphocytes and macrophages has been noted in regressing lesions. One of the dose limiting toxicities of rIL-2 is the development of a capillary leak syndrome attributed to widespread endothelial activation. Changes in expression of endothelial and leucocyte-associated adhesion molecules were assessed in tumour and uninvolved skin in patients with metastatic breast cancer receiving rIL-2. Increased expression of intracellular adhesion molecule-1, its leucocyte-associated ligand, leucocyte function associated molecule-1, vascular cell adhesion molecule and its ligand, very late after activation antigen-4 as well as members of the selectin family of adhesion molecules, were noted in uninvolved skin following rIL-2. Expression of these adhesion molecules was noted in tumour stroma before rIL-2 but little change was observed following rIL-2 infusion. An influx of monocytes and T-lymphocytes (expressing the IL-2 receptor and of the memory subtype) and a lower number of neutrophils was noted in uninvolved skin following rIL-2. Although monocytes and T-lymphocytes were present in tumour stroma before rIL-2 no changes were observed following infusion. The changes noted in the dermis contrast with those seen at tumour sites and may partly explain the low therapeutic index of rIL-2.
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PMID:Adhesion molecule expression and leucocyte trafficking following immunotherapy with recombinant interleukin-2. 873 38

Direct multi-colour flow cytometric analysis was employed in patients with Graves' disease (n = 10) to determine the immunophenotype in peripheral blood lymphocytes (PBL) at the time of diagnosis without treatment (PBLw) and prior to operation (PBLp) and in thyroid-derived lymphocytes (TL). Additionally, the secretion of anti-thyroperoxidase antibodies (anti-TPO) was measured during culture of isolated peripheral or thyroid-derived B cells. Among TL from patients with high serum levels of anti-TPO (6/10) a significantly (p < 0.01) higher percentage of B cells were detected compared to PBLp (TL: 21.7 +/- 7.2%; PBLp: 13.2 +/- 4.5%). Enriched thyroid-derived B cells only from these patients also showed high spontaneous anti-TPO secretion during culture. The difference between peripheral and thyroid-derived natural killer (NK) cells was highly significant (p < 0.001; TL: 5.6 +/- 6.3%; PBLp: 13.6 +/- 5.5%). Two patients were found with a higher number of NK cells within TL. These patients were among those who had a low number of B cells infiltrating the thyroid gland. Regarding the expression of several other differentiation antigens, i.e. CD4 and CD8, gamma/delta TCR bearing T cells and CD45R0 on CD4+ T cells as a marker for memory cells, on TL no differences could be detected between patients with or without anti-TPO. In TL 31.5 +/- 7.7% of CD3- cells expressed the HLA-DR antigen (vs. 6.1 +/- 2.4% in PBLp; p < 0.001). Half of these cells simultaneously expressed the activation antigen CD69. Surprisingly, the number of CD3+ TL bearing the IL-2 receptor (CD25) and transferrin receptor (CD71) was not increased. Taken together, the proportional distribution of B and NK cells within the thyroid correlates with the anti-TPO secretion in vivo and in vitro, suggesting different immune response regulation processes of TL.
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PMID:Different immunophenotype and autoantibody production by peripheral blood and thyroid-derived lymphocytes in patients with Graves' disease. 875 May 71


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