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

The requirements for the conversion of CD8+ memory T cells into effector class I major histocompatibility complex (MHC) Kd-restricted cytotoxic T (Tc) cells in vitro have been studied. Purified CD8+ splenocytes from influenza A/WSN-primed BALB/c (H-2d) mice stimulated with a synthetic nucleoprotein peptide 147-158 R156- (NPP) alone generated Tc cells specific for influenza virus-infected target cells. No additional requirements for accessory cells or their lymphokine products were necessary indicating that peptide antigen (Ag) in association with Kd was presented on CD8+ T cells. The evidence for presentation of NPP by CD8+ T cells was supported by the use of CD8+ memory T cells from semiallogeneic bone marrow radiation chimeras of P1----F1 type (H-2b----[H-2d x H-2b]F1). Memory CD8+ splenocytes from A/WSN-immune chimeras did not develop into secondary effector Tc cells as a result of a 4-day culture with NPP alone, however, were able to do so if NPP was presented by Kd-bearing Ag-presenting cells. In addition, these results exclude the possibility of direct recognition of free NPP molecules by the specific T cell receptor of CD8+ memory T cells. CD8+ memory splenocytes (H-2b) from chimeras were also able to develop into functionally active Tc cells as a result of presentation of Db-restricted synthetic peptide (NP 366-374) with a sequence derived from influenza virus nucleoprotein with high affinity for Db MHC class I molecules. Blockade of endogenously produced interleukin 2 (IL-2) activity by anti-IL-2 or anti-IL-2 receptor monoclonal antibody in the culture of CD8+ memory T cells during a 4-day NPP stimulation completely abolished Tc cell generation, indicating that the utilization of this lymphokine is absolutely required for the secondary Tc cell development. These findings demonstrate that CD8+ memory T cells per se are able to recognize the restimulating epitope as a result of its presentation by CD8+ T cells and develop into cytolytically active and highly specific Tc cells with no requirements for other cellular helper components or their lymphokine products.
 ...
PMID:Specific epitope-induced conversion of CD8+ memory cells into effector cytotoxic T lymphocytes in vitro: presentation of peptide antigen by CD8+ T cells. 137 66

The role of uncultured melanoma cells in the proliferation of autologous tumor-specific cytotoxic T lymphocytes (CTLs) was investigated. Uncultured autologous tumor cells by themselves induced modest, but significant, proliferation in 10 of 13 (77%) CTL clones and in only two of nine non-CTL clones. Uncultured allogenic melanoma cells mostly failed to induce CTL proliferation. Autologous tumor-induced CTL proliferation declined with increasing age of the culture. It did not correlate with IL-2 receptor-alpha expression or was not inhibited by addition of anti-IL-2 antibody to the culture. It was inhibited by pretreatment of tumor cells with anti-MHC class II, but not -MHC class I mAb. IL-2 alone was sufficient for the potent proliferation of five of nine CTL clones. In all these five CTL clones, autologous tumor cells suppressed IL-2-induced proliferation. The remaining four CTL clones, however, required both uncultured autologous melanoma cells and IL-2 for the proliferation. IL-4 or IL-6, in particular IL-6, facilitated IL-2-induced CTL proliferation, but not their cytotoxicity. In summary, uncultured melanoma cells by themselves induced modest levels of CTL proliferation in the context of MHC class II antigens, whereas they suppressed IL-2-induced CTL proliferation in more than half of the clones.
 ...
PMID:Role of uncultured human melanoma cells in the proliferation of autologous tumor-specific cytotoxic T lymphocytes. 162 65

The immunological study of the major histocompatibility complex (class I, class II and DR antigens), tumour infiltrating lymphocytes (TIL), regional lymph node lymphocytes (RLNL) and peripheral blood lymphocytes (PBL) was evaluated on the basis of immunohistochemical staining using monoclonal antibodies of each subset of lymphocytes in a series of 16 patients with renal cell carcinoma. Two renal cell carcinomas in dialysis patients with acquired cystic disease of the kidneys (ACDK) were also included in this study. With regard to the immunological environment, a comparative study between renal cell carcinoma accompanied with ACDK and 14 other renal cell carcinoma was carried out. The results are described below: 1) With regard to the expression of MHC antigens in tumour cells, the degrees of expression of MHC class I, class II and DR-antigen in case 1 were higher than that of the other 14 renal cell carcinomas. On the other hand, no expression of MHC was detected in case 2. 2) As to the subsets of TIL, the CD25 (IL-2 receptor) was not expressed in all the renal cell carcinoma. As to the T cell receptor (TCR-alpha/beta chain), the degree of expression was the same in case 1 and the other 14 cases. On the other hand, no TCR was detected in the case 2. As to the other subsets of TIL (CD3, CD4, CD8, CD16 and CD20), the rates of the infiltration were the same in case 1 and the other 14 cases, but those in case 2 were lesser than in all other 14 cases.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Immunological study on renal cell carcinoma in dialysis patients with acquired cystic disease of kidneys]. 176 69

The potential of cells within the central nervous system (CNS) to initiate T lymphocyte responses is not known and was the subject of this study. Using the ability of virgin T lymphocytes to proliferate in a primary response to allogeneic determinants on antigen-presenting cells (APC), we have examined the capacity of major histocompatibility complex (MHC)-expressing astroglial cells to act as stimulators of primary and secondary T cell responses. Neither freshly isolated astrocytes nor primary astrocyte cultures pretreated with interferon gamma (IFN-gamma) to upregulate MHC class I and II expression stimulated unfractionated lymph node (LN) cell populations in the primary mixed lymphocyte reaction. In mixing experiments, astrocytes did not inhibit the T cell response to allogeneic LN stimulators. Purified responder CD4+ T cells also were not stimulated to proliferate or secrete interleukin 2 (IL-2) by MHC class I- and II-expressing astrocytes. In contrast to their inability to stimulate virgin, alloreactive CD4+ T cells, astrocytes were able to specifically stimulate an alloreactive CD4+ T cell line. Unprimed CD8+ T cells, however, exhibited some weak autonomous proliferation to astrocyte stimulators but this response was only substantial in the presence of exogenous IL-2, the latter predominantly being a CD4+ T cell product. Those CD8+ T cells responding in the presence of IL-2 were mainly T cell receptor alpha/beta+ IL-2 receptor (alpha chain)+, and a majority had shifted from high to low CD45R expression. Given the virtual dependence of CD8+ T cells in these studies, on CD4+ T cell help, and the complete absence of activation of this latter subset by astrocytes, it is clear that in the context of this resident CNS cell, further activation of either T cell subset by astrocytes within the CNS can only follow priming by another type of APC. The implications of these results for the induction of T cell responses in the CNS are discussed.
 ...
PMID:Major histocompatibility complex-expressing nonhematopoietic astroglial cells prime only CD8+ T lymphocytes: astroglial cells as perpetuators but not initiators of CD4+ T cell responses in the central nervous system. 182 42

The aim of the present work was to study regulatory interactions between MHC class I molecules and the interleukin (IL)-2, IL-3, and IL-4 receptors and functional interactions between the receptors for IL-2 and IL-4. Our major observations were: (1) quiescent splenic T cells exposed to specific anti-MHC class I antibodies become responsive to IL-2 and IL-4 stimulation; (2) T-cell clones (CTLL-2 and HT-1) grown at high cell density or low IL-2 concentrations become refractory to IL-2 and IL-4 stimulation. After exposure to anti-class I antibodies the refractory cells recover responsiveness to lymphokine-induced proliferation; (3) IL-2 receptor expression is non-inducible in class I-negative T-lymphoma cells, but is inducible following class I gene transfection of the cells; (4) exposure of T-cells and clones to IL-2 receptor antibody increases the responsiveness to IL-4 stimulation; (5) IL-2 and IL-4 act synergistically at low and substimulatory lymphokine levels; and (6) IL-3 responsiveness of hemopoietic cells is not influenced by exposure to anti-MHC class I antibody. It is concluded that class I molecules are of importance for the functional expression of the receptors for IL-2 and IL-4 and that these receptors are functionally interrelated.
 ...
PMID:T-cell activation. IV. Evidence for a functional linkage between MHC class I, interleukin-2 receptor, and interleukin-4 receptor molecules. 183 52

A functional analysis of tumor-infiltrating lymphocytes (TILs) from renal cell carcinoma (RCC) and malignant melanoma was performed. TILs were expanded in recombinant interleukin-2 (50 U/ml) in Iscoves medium. Phenotypic and functional (cytolytic vs regulatory) analyses were carried out with the fresh and expanded TIL populations after 4 weeks in culture. Only one TIL population from an RCC case (out of six cases studied) was CD8+ and demonstrated MHC class I-restricted tumor-specific cytotoxicity against the autologous RCC target. TIL populations from the other five cases became predominantly CD4+ and they neither killed the respective autologous tumor cells nor killed the NK-sensitive target K-562 cells. When studied for other functions, two CD4+ TIL populations were found to suppress the lymphokine-activated killer cell response by peripheral blood lymphocytes (PBL) in coculture. Of these two, a TIL population from an RCC case (MJ TIL) was used to study the cellular and molecular mechanisms of suppression. The MJ TIL synthesized a supernatant factor that blocked activation of resting PBL as measured by the induction of high-affinity IL-2 receptor (IL-2R) when stimulated by phytohemagglutinin but did not down-regulate the fully expressed IL-2R on activated T cells. The suppression of high-affinity IL-2R induction on T cells did not result from tumor necrosis factor-alpha and beta or from transforming growth factor-beta as these cytokines were not detected in the cell-free supernatant from the MJ TIL culture. The supernatant factor also suppressed IL-2-mediated enhancement of cytotoxicity by natural killer (NK) cells without demonstrating direct toxic effect on the NK cells. Thus, when TIL are used for adoptive immunocytotherapy, it may be useful to fully characterize them functionally, in vitro.
 ...
PMID:Suppression of lymphokine-activated killer cell generation by tumor-infiltrating lymphocytes. 202 93

The present work demonstrates that antibody-induced cross-linking of MHC class I antigens on Jurkat T lymphoma cells leads to a rise in intracellular calcium (Cai2+) and, in the presence of phorbol ester (PMA), to IL-2 production and IL-2 receptor expression. The rise in Cai2+ exhibited a profile very different from that obtained after anti-CD3 antibody-induced activation suggesting that activation signals are transduced differently after binding of anti-CD3 antibody and class I cross-linking, respectively. However, when Cai2+ was examined in individual Jurkat cells by means of a digital image processing system no differences were observed after cross-linking with anti-CD3 and anti-MHC class I antibodies, respectively. Two CD3-negative mutant lymphoma lines were nearly totally refractory to class I cross-linking. Taken together our results may indicate the existence of a functional linkage between the T cell receptor complex and MHC class I molecules.
 ...
PMID:T cell activation. II. Activation of human T lymphoma cells by cross-linking of their MHC class I antigens. 213 76

The aim of this study was to examine whether the unresponsiveness of MHC class I-negative subclones of the EL4 thymoma to CD3 cross-linking can be restored by transfection of class I genes into the H-2-negative cells. Cell activation experiments with selected MHC class I-negative subclones and H-2b- and H-2Ld-positive transfectants showed that these cells are equally capable of secreting interleukin 2 (IL-2) after exposure to the phorbol ester phorbol 12-myristate 13-acetate (PMA) and ionomycin. In contrast, only the parental H-2-positive EL4 cells are capable of responding to treatment with immobilized anti-CD3 antibody with IL-2 secretion and IL-2 receptor expression. Measurements of intracellular free Ca2+ (Ca2+i) following anti-CD3 antibody-induced cross-linking of parental EL4 cells and H-2-negative and H-2b gene-transfected subclones showed that the parental cells and two of the class I transfectants, one H-2-positive and one H-2-negative, responded with a slow rise in Ca2+i, whereas one H-2-positive transfected cell clone was completely refractory to CD3 cross-linking. Modulation experiments using parental EL4 cells, H-2-negative subclones and H-2-positive transfectants demonstrated that the CD3 and class I molecules of these different cells are modulated to the same extent after exposure to specific antibodies. The present findings thus indicate that the unresponsiveness of H-2-negative EL4 subclone cells to CD3 cross-linking is not functionally associated with a lack of class I surface expression.
 ...
PMID:T-cell activation. III. Attempts to activate MHC class I-negative and class I-transfected EL4 T-lymphoma cells by immobilized anti-CD3 antibody. 214 10

Interleukin-2 (IL-2) plays an essential role in the clonal expansion of antigen-activated T lymphocytes (T cells). In fact, the expression of both IL-2 and IL-2 receptor (IL-2R, p55, CD25) genes is transiently induced upon T cell activation through the interaction of antigen/major histocompatibility complex (MHC) and T cell receptor complex. To elucidate the mechanism(s) of the induced gene expression for IL-2 and IL-2R, we have investigated for the presence of potential transcription factors that specifically interact with regulatory cis-elements. Here, we demonstrate that one such factor mediates the induced expression of both genes. Interestingly, the recognition sequences by this factor are significantly diverse in these two genes and are related to those of immunoglobulin (Ig) kappa chain and MHC class I genes. We provide evidence that this factor indeed binds to the IL-2, IL-2R, and Ig sequence elements with different affinities, thereby affecting the magnitude of gene expression. Interestingly, this factor also binds to other cytokine genes, such as interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and HIV-1 and HTLV-1 LTR sequences.
 ...
PMID:Involvement of a common transcription factor in the regulated expression of IL-2 and IL-2 receptor genes. 251 55

To investigate the possible involvement of some cell surface structures on lymphoid cells in the functional activity of lymphokine activated killer (LAK) cells, a number of monoclonal antibodies (Mab) against such structures was studied for their ability to inhibit LAK activity in a standard cytotoxicity assay against the natural killer-insensitive target cell EL-4. Almost complete inhibition of LAK activity resulted from incubation with antibodies to the LFA-1 antigen, while blocking of the Lyt 2 antigen reduced cytotoxic activity about 50%. Mab to T-200 gave a weak and inconsistent inhibitory activity, while antibodies to Thy 1, L3T4, IL-2 receptor and MHC class I antigens were without effect. Mab to LFA-1 and Lyt 2 inhibited LAK activity towards EL-4, YAC-1 and differentiated F-9 teratocarcinoma cells, but did not affect LAK-mediated killing of undifferentiated F-9 cells. Experiments with separate preincubation of effector and target cells revealed that both LFA-1 and Lyt 2 inhibited LAK activity at the effector cell level only.
 ...
PMID:Functionally involved cell surface antigens on murine lymphokine activated killer cells. 329 81


1 2 3 4 Next >>