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

The CD4 molecule plays an essential role in antigen-induced activation of T helper (Th) cells, but its contribution to signal transduction events resulting in physiologic T cell function is ill defined. By utilizing anti-CD4 monoclonal antibodies (MAbs) that recognize distinct epitopes of CD4, we have investigated the role of CD4 molecule in antigen-induced interleukin 2 (IL-2) and IL-2 receptor (IL-2R) alpha chain expression in class II major histocompatibility complex-restricted antigen-specific human Th clones. Pretreatment of the Th clones with Leu3a resulted in a dose-dependent suppression of antigen-induced proliferative responses, inositol phosphate accumulation, increase in free cytoplasmic calcium ions ([Ca2+]i), IL-2 mRNA accumulation, IL-2 secretion, and membrane IL-2R expression. IL-2R mRNA accumulation, however, was unaffected even at highest Leu3a concentrations. Leu3a treatment did not affect bypass activation of T cells with PMA plus ionomycin or activation via CD2 molecule. The MAb OKT4, which binds another domain of CD4, was not inhibitory. These results suggest that after T cell antigen receptor-CD3 activation, IL-2 gene induction, IL-2 secretion, and membrane IL-2R expression are absolutely dependent upon participation of CD4 molecules, phosphatidylinositol (PI) hydrolysis, and increase in [Ca2+]i. The requirement for IL-2R gene induction, however, occurs independently of CD4 molecule participation and PI hydrolysis.
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PMID:Role of CD4 molecule in the induction of interleukin 2 and interleukin 2 receptor in class II major histocompatibility complex-restricted antigen-specific T helper clones. T cell receptor/CD3 complex transmits CD4-dependent and CD4-independent signals. 153 18

Resting natural killer (NK) cells express the p75 chain of the IL-2 receptor (IL-2R beta) and most NK cells express the CD2 (erythrocyte rosette) receptor. The cell adhesion molecule, LFA-3, is a natural co-ligand for CD2. Tac antigen (IL-2R alpha), a p55 IL-2R subunit, can be expressed after NK activation and may play a role in IL-2-induced NK proliferation. Little is known of the molecular mechanisms underlying cytokine production in NK cells. We investigated the roles of IL-2R alpha, IL-2R beta, and CD2/LFA-3 in the molecular regulation of NK cell granulocyte/macrophage-colony-stimulating factor (GM-CSF) production. Enriched populations of peripheral blood NK cells were separated into CD16-positive and CD16-negative fractions by flow cytometry; positively selected cells were greater than 97% positive for CD16 (the FcIII receptor for IgG which is present on almost all NK cells), less than 1% positive for the T cell antigen CD3, and did not demonstrate rearrangement of the T cell receptor beta chain gene by Southern blot. NK cell supernatants were harvested after 3-4 d of incubation with 0-100 U/ml IL-2, or after incubation with anti-CD2 (T11(3] MAb and sheep red blood cells (SRBC are a homologue for LFA-3). Parallel cell aliquots were harvested at 3-16 h for transcriptional run-on assays, S1 nuclease assays, and actinomycin D mRNA t1/2 determinations. IL-2-activated NK supernatants contained large amounts of GM-CSF (178 +/- 35 pg/ml) by ELISA as did supernatants from CD2-activated NK cells (T11(3) MAb + SRBC: 212 +/- 42) vs. less than 20 pg/ml for NK cells incubated alone or with either SRBC or T11(3) MAb alone. Sepharose-linked anti-CD3 MAb did not induce GM-CSF release from NK cells. By S1 analysis, both IL-2 and CD2 stimulation markedly augmented GM-CSF mRNA expression but with very different latencies of onset. IL-2R beta MAb inhibited greater than 85% of GM-CSF release from IL-2-activated NK cells and markedly suppressed IL-2-induced GM-CSF mRNA expression, whereas IL-2R alpha MAb even at 2,000-fold molar excess of IL-2 had little effect (less than 10%) on either GM-CSF release or mRNA expression. Run-on assays showed that GM-CSF is constitutively transcribed in NK cells and that IL-2 and CD2-activated cells had a three- to fourfold increased rate of GM-CSF transcription compared to nonstimulated cells. The t1/2 of GM-CSF mRNA in IL-2-activated NK cells was identical to that of unstimulated NK cells (15 min), whereas GM-CSF mRNA t1/2 in CD2-activated NK cells was increased 2.5-fold. We conclude that GM-CSF production in NK cells is regulated by both the IL-2Rbeta and the CD2 receptor but not by IL-2Ralpha, that both transcriptional and posttranscriptional signals act together to modulate the level of GM-CSF mRNA in NK cells, and that the molecular mechanisms underlying NK cell GM-CSF production are dependent in part on differential surface receptor activation.
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PMID:Production of granulocyte/macrophage-colony-stimulating factor by human natural killer cells. Modulation by the p75 subunit of the interleukin 2 receptor and by the CD2 receptor. 167 38

Cellular immunity was investigated in 43 patients with multiple myeloma (MM) by assessing 3HTdR uptake induced by monocyte-dependent [CD3 monoclonal antibodies (MoAbs), phytohemagglutinin (PHA)] and monocyte-independent (CD2 MoAbs, ionomycin + phorbolester) stimulations. The former were evaluated in peripheral blood mononuclear cells (PBMNC) and purified T cells; the latter were evaluated in purified T-cell preparations only. MM showed significantly lower PBMNC responses to PHA (P less than .001), soluble OKT3 (CD3) (P = .01), and immobilized OKT3 MoAbs (P = .01). On purification of T cells, MM responses were still defective to soluble T11(2) + T11(3) (CD2) MoAbs (P = .004), phorbol myristate acetate (PMA) plus ionomycin (P less than .001), but significantly higher to plastic-immobilized OKT3 (P = .004). In some MM, 3HTdR uptake, interleukin-2 (IL-2) receptor (CD25) expression, and IL-2 production were as high on stimulation with plastic-immobilized OKT3 as that observed in normal subjects under optimal conditions (ie, plastic-immobilized OKT3 plus accessory signals). CD3 hyperreactivity correlated with the number of CD8+ HLA-DR+ cells in MM T-cell preparations. MM patients with more than 10% CD8+ HLA-DR+ cells had significantly higher responses to immobilized OKT3 (P less than .001), but lower responses to T11(2) plus T11(3) (P = .01), and PMA plus ionomycin (P = .03) than patients with less than 10% CD8+ HLA-DR+ cells. Phenotyping of CD45RA (naive) and CD45R0 (memory) expressions in resting MM T cells showed a lower ratio of CD45RA to CD45R0 in both CD4 (P less than .05) and CD8 (P less than .001) subpopulations. These data indicate that (a) some MM T cells require significantly fewer accessory signals (if any) to express the IL-2 receptor fully, secrete IL-2, and proliferate on multivalent cross-linking of the CD3/TCR complex; and (b) this peculiar state of activation is associated with high HLA-DR expression in CD8+ lymphocytes.
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PMID:Detection of hyperreactive T cells in multiple myeloma by multivalent cross-linking of the CD3/TCR complex. 156 45

Patients who undergo allogeneic bone marrow transplantation (BMT) are clinically immunodeficient for a prolonged period after engraftment. In the present study, we examined immune function after BMT in a series of patients who had received HLA compatible sibling marrow grafts purged of T cells with anti-CD6 monoclonal antibody and complement. None of the patients in this analysis received immunomodulating agents and none had developed graft-versus-host disease (GVHD). Initially after BMT, natural killer (NK) cells are the predominant cell type, giving way to CD3+, CD5+ T cells after 4 to 8 weeks. Despite the return of normal numbers of T lymphocytes post-BMT phenotypic analysis reveals several long-term abnormalities, including an inverted T4:T8 ratio and a significant fraction of CD3+ T cells that do not co-express CD6. In mitogenic assays, stimulation by either nonspecific lectin (phytohemagglutinin; PHA) or antibodies to the CD2 surface structure (anti-T11(2) + anti-T11(3)) results in decreased levels of T-cell proliferation compared with controls for over 18 months post-BMT. In contrast, the ability of unstimulated peripheral blood mononuclear cells (PBMC) to respond to recombinant interleukin-2 (rIL-2) is relatively intact, most likely reflecting early functional reconstitution of the NK cell population. To further characterize the prolonged abnormalities in T-cell proliferation after PHA or CD2 stimulation, we examined more proximal events in T-cell activation such as induction of IL-2 receptor expression and stimulus-induced intracellular calcium flux. We found that the induction of IL-2 receptor (p55) after in vitro activation, although initially abnormal, recovers completely by 6 months post-BMT. We also found that, after CD2 stimulation, calcium flux in T cells was normal immediately after engraftment. In contrast, after stimulation with anti-CD3 antibodies, a large population of T cells do not develop intracellular calcium flux compared with controls. We conclude that despite the recovery of normal numbers of T lymphocytes early after engraftment of CD6-depleted marrow, these T cells exhibit several physiologic and functional abnormalities that persist for varying intervals post-BMT. At present, it is unclear which of these specific defects is most closely associated with increased susceptibility to infectious agents after BMT.
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PMID:Reconstitution of T-cell function after CD6-depleted allogeneic bone marrow transplantation. 197 Sep 38

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

In this study the effect of anti-cluster designation (CD) 2 monoclonal antibodies (mAb) on the activation of a cloned human T cell line, HY837, after triggering the CD3/T cell receptor (TcR) complex by anti-CD3 or anti-TcR mAb is described. HY837, which reacts with a series of mAb directed at different epitopes on the TcR, could be induced to proliferation and interleukin 2 (IL-2) production by soluble mAb directed at the CD3/TcR complex in the absence of accessory cells. mAb directed at the CD2 epitope T11-1 were shown to block the IL-2 production by HY837, as well as the expression of the IL-2 receptor, induced by anti-CD3 mAb, resulting in the inhibition of the proliferative response. The effect of anti-CD2 mAb on the proliferative response of HY837, induced by anti-CD3 mAb, was not due to a competition for Fc binding sites. In contrast, the proliferative responses and IL-2 production of HY837, induced by mAb directed at the TcR, were shown to be enhanced by the action of the anti-CD2 mAb. These results indicate that effects mediated by anti-CD3/TcR mAb cannot always be extrapolated to antigen-mediated effects and show that anti-CD2 mAb may regulate the T cell response, induced by mAb directed at the CD3/TcR complex, depending on which part of this complex is triggered during activation.
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PMID:Regulation by anti-CD2 monoclonal antibody of the activation of a human T cell clone induced by anti-CD3 or anti-T cell receptor antibodies. 244 43

The role of distinct regions of HLA class I molecules in regulating T-cell activation via the CD3-antigen receptor complex was investigated. Monoclonal antibodies (MoAbs) which recognize monomorphic and polymorphic epitopes on HLA Class I molecules were shown to inhibit T-cell proliferation to OKT3. These MoAbs have differential effects on the synthesis of interleukin-2 (IL-2) and IL-2 receptor expression. Cell cycle analysis demonstrated that these MoAbs function both in inhibiting cell cycle entry (G0-G1 shift) and in blocking cell cycle progression (G1-S shift) of activated T cells. Furthermore, these MoAbs have regulatory effects on the alternate pathway of T-cell activation via the CD2 molecule, T-cell activation induced by PHA, and activation induced by the phorbol ester PMA in conjunction with the calcium ionophore Ionomycin. Thus these MoAbs have different effects depending upon the pathway of T-cell activation. The results indicate that HLA class I molecules are selectively involved in the sequence of intracellular events leading to T-cell activation and proliferation.
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PMID:CD3 pathway of T-cell activation. II. Role of HLA-class I molecules in early events. 245 48

The addition of autologous erythrocytes to unfractionated human mononuclear cell cultures results in enhancement of B cell responses to antigens and mitogens. This costimulating effect of red cells is abrogated by their preincubation with anti-LFA-3 monoclonal antibody. Preincubation of mononuclear cells with anti-CD2 monoclonal antibodies (anti-Leu 5b, OKT11, used singly) has a down-regulating effect on B cell activation and no enhancement of B cell responses is seen when red cells are added to anti-CD2-treated cultures. These results demonstrate a functional effect on B cells of the interaction between the CD2 molecule on T lymphocytes and its natural ligand, LFA-3. The precise mechanism by which this costimulating effect on B lymphocytes takes place is unclear. The study of T cell populations and T cell activation markers shows that the addition of erythrocytes causes a small but reproducible increase in the number of cells expressing the IL-2 receptor and the addition of IL-2 enhances the response of mononuclear cells to antigenic stimulation in the presence of erythrocytes. However, the supernatants of mononuclear cell cultures stimulated with pokeweed mitogen in the presence of autologous erythrocytes show decreased levels of IL-2, compared to supernatants of cells stimulated with pokeweed mitogen alone. The same supernatants show increased levels of interferon-gamma, but the addition of this lymphokine to cultures stimulated with pokeweed mitogen has no potentiating effect. It is possible that the effect of erythrocytes is mediated by other growth and/or differentiation factors, and additional studies will be required to clarify this point.
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PMID:The interaction of CD2 with its LFA-3 ligand expressed by autologous erythrocytes results in enhancement of B cell responses. 246 Feb 48

Activation of human-purified T cells can be mediated by pairwise combinations of monoclonal antibodies directed against T11.1 and T11.2 epitopes on the CD2 molecule. Monoclonal antibodies (mAbs) reactive with either the alpha and beta chains of the lymphocyte-function-associated antigen-1 (LFA-1) molecule or one of its ligands, intercellular adhesion molecule-1 (ICAM-1), were found to accelerate anti-CD2-induced proliferation. This effect was seen on thymocytes and resting or preactivated T cells (phytohemagglutinin blasts and alloproliferative T cell clones) and could be observed, following the introduction of anti-LFA-1 or -ICAM-1 mAbs, up to 50 hr after the CD2 stimulatory signal. This effect was equally abrogated by 55 kDa anti-interleukin-2 (IL-2) receptor mAb, but neither the expression of IL-2 receptor nor the production of IL-2 was modified. The effects of anti-LFA-1 or anti-ICAM-1 on T cell activation through the CD2 pathway were therefore opposite to those observed in the CD3 pathway, where both mAbs strongly delayed T cell proliferation.
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PMID:Monoclonal antibodies against LFA-1 or its ligand ICAM-1 accelerate CD2 (T11.1 + T11.2)-mediated T cell proliferation. 257 21

T cells can be divided into unprimed virgin (T0) and primed memory (T') subpopulations by their expression of different isoforms of the leukocyte common antigen. We have separated the CD4+ T cells into T0 and T' subpopulations and examined their capacity to respond to activation signals via the CD2 receptor molecule. On stimulation with a mitogenic combination of anti-CD2 antibodies, the T' population was induced to express IL-2 receptor, increased levels of the 4F2 antigen and to proliferate, whereas the response of the T0 populations was reflected solely by a minimal increase in the 4F2 antigen. The addition of IL-2 or monocytes to T0 cells stimulated with anti-CD2 antibodies did not enhance their expression of the IL-2 receptor or proliferation. However, T0 cells stimulated with the triad of anti-CD2 antibodies, monocytes, and IL-2 responded with high levels of IL-2 receptor expression and proliferation. The T0 subpopulation could also be induced to respond when cultured with anti-CD2 antibodies and phorbol myristate acetate. The results suggest that in order to respond to stimulation via the CD2 molecule, virgin T helper cells require additional signals that can be jointly provided by monocytes and IL-2. In contrast, memory T helper cells can be activated via CD2 signal transduction alone.
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PMID:Virgin and memory T cells have different requirements for activation via the CD2 molecule. 257 87


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