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)

In this study we identify and characterize a subset of human peripheral blood T cells, present in all individuals, that has features previously described for T cells either separately or in special circumstances. These cells are found in purified suspensions of resting peripheral blood lymphocytes within the CD8+ T lymphocytes, express alpha beta T cell receptor (TCR), and can be identified and isolated because of high-density expression of surface CD11b (TCR alpha beta +/CD3+/CD8+/CD11b+ cells). They coexpress constitutively the IL-2 receptor beta chain, Fc gamma RIIIA, and CD56. Although they do not mediate spontaneous cytotoxicity, CD3+/CD8+/CD11b+ cells have cytotoxic potential, demonstrated in redirected cytotoxicity assays with P815 target cells in the presence of anti-Fc gamma RIII (CD16) or anti-CD3 monoclonal antibodies. Stimulation of CD3+/CD8+/CD11b+ cells with rIL-2 induces proliferation, cytotoxicity against NK-sensitive and NK-resistant target cells, and expression of surface activation antigens, including IL-2 receptor alpha chain (CD25). CD3+/CD8+/CD16+/CD56+ cell clones with cytotoxic functions including those mediated by engagement of surface CD16 were obtained by limiting-dilution cloning of purified CD3+/CD8+/CD11b+ cells in the presence of rIL-2 and autologous feeder cells. Our data support the hypothesis that the CD3+/CD8+/CD11b+/CD16+ cells represent a discrete peripheral blood lymphocyte subset that could be the physiological counterpart of that expanded in several pathological conditions and in large granular lymphocyte lymphocytosis.
 ...
PMID:Coexpression of Fc gamma receptor IIIA and interleukin-2 receptor beta chain by a subset of human CD3+/CD8+/CD11b+ lymphocytes. 768 65

T cell receptor stimulation without costimulation is insufficient for the induction of an optimal immune response. It is thought that engagement of the CD28 molecule with its ligand B7 provides an essential costimulatory signal without which full activation of T cells cannot occur. A mouse strain with a defective CD28 gene was established. Development of T and B cells in the CD28-deficient mice appeared normal. However, T lymphocytes derived from CD28-/- mutant mice had impaired responses to lectins. Lectin stimulation did not trigger interleukin-2 (IL-2) production, IL-2 receptor alpha expression was significantly decreased, and exogenous IL-2 only partially rescued the CD28 defect. Basal immunoglobulin (Ig) concentrations in CD28-deficient mice were about one-fifth of those found in wild-type controls, with low titers of IgG1 and IgG2b but an increase in IgG2a. In addition, activity of T helper cells in CD28-/- mice was reduced and immunoglobulin class switching was diminished after infection with vesicular stomatitis virus. However, cytotoxic T cells could still be induced and the mice showed delayed-type hypersensitivity after infection with lymphocytic choriomeningitis virus. Thus, CD28 is not required for all T cell responses in vivo, suggesting that alternative costimulatory pathways may exist.
 ...
PMID:Differential T cell costimulatory requirements in CD28-deficient mice. 768 39

Large granular lymphocytes (LGLs) could be generated in vitro from tumor-associated cells (TACs) derived from the rhabdomyosarcoma, 76-9, but only after treatment of the tumor bearers with cyclophosphamide (CY). The ability to generate LGLs in vitro was dependent on the presence of high concentrations of recombinant interleukin (rIL)-2 and related to the phase of tumor regression induced by CY. Maximum yields of LGLs were obtained when TACs were derived on days 7 or 8 after CY injection. TACs derived on day 8 and grown in rIL-2 for 5 days were shown to express NK 1.1, B220, IL-2 receptor (IL-2R), Thy-1.2 and a late NK cell differentiation antigen identified by monoclonal antibody, 4H12. They did not express MAC-1, CD3, alpha/beta T cell receptor, CD4 or an early NK cell differentiation antigen identified by monoclonal antibody, 3C2. The expression of NK 1.1, B220, IL-2R, Thy-1.2 and 4H12 by TACs growing in rIL-2 was relatively stable over a 12-day period. IL-2-activated TACs were shown to lyse YAC-1 cells, the wild-type 76-9 tumor cells and two clones of the 76-9 tumor, as well as cells from an independently derived sarcoma, 77-23. Intratumor injection of IL-2-activated TACs or rIL-2 after CY injection induced a significant delay in the recurrence of tumor growth. The data suggest that the increase of IL-2-reactive cells after CY injection and their intratumor disposition may indicate a potential for in situ antitumor effects.
 ...
PMID:Changes in tumor-associated NK 1.1+ large granular lymphocyte precursors after cyclophosphamide injection: in vitro characterization and potential therapeutic application. 783 24

T lymphocytes bearing the gamma/delta T-cell receptor are a rare component of normal human GI epithelium and skin. Recently, however, an unusually high percentage of T lymphocytes with gamma/delta receptors has been described in gastrointestinal biopsies from patients with dermatitis herpetiformis, implicating the gamma/delta T cell subset in the pathogenesis of this disease. We investigated a possible role for this subset of lymphocytes in the pathogenesis of the cutaneous lesions of dermatitis herpetiformis. Using a standard immunoperoxidase technique, we labelled perilesional skin biopsies from patients with dermatitis herpetiformis and other inflammatory dermatoses with monoclonal antibodies to CD3, CD4, CD8, alpha/beta T cell receptor, gamma/delta T cell receptor, and IL-2 receptor. We found no differences in the percentage of gamma/delta positive T lymphocytes in skin lesions of dermatitis herpetiformis as compared to other selected inflammatory conditions. These findings suggest that the pathogenesis of the cutaneous lesions of dermatitis herpetiformis is not mediated through gamma/delta T cells, and that the cutaneous lesions may develop through mechanisms different from those operative in the gastrointestinal tract.
 ...
PMID:T lymphocytes bearing the gamma/delta T-cell receptor in cutaneous lesions of dermatitis herpetiformis. 786 53

We have used a murine model of organ-specific autoimmunity to characterize therapeutic modalities capable of down-regulating the cellular limb of the autoimmune response. Murine interstitial nephritis is an autoimmune disease mediated by tubular antigen-specific CD8+ nephritogenic effector T cells which are delayed-type hypersensitivity (DTH) reactive and cytotoxic to renal epithelial cells. Previous studies have demonstrated that disease can be suppressed with experimentally induced populations of T cells (Ts1 and Ts2 cells) obtained after injection of tubular antigen-coupled splenocytes into syngeneic mice. As the target of Ts2 is the CD8+ effector T cell, we have evaluated its effects on nephritogenic effector T cell clones isolated from diseased animals. Our studies demonstrate that soluble proteins expressed by Ts2 cells (TsF2) specifically abrogate the DTH, cytotoxic, and nephritogenic potential of M52 cells, although T cell receptor and IL-2 receptor expression are unchanged in these unresponsive M52 clones. TsF2-induced inhibition is dependent on new mRNA and protein synthesis. In a cytotoxic clone, M52.26, exposure to TsF2 induces expression of TGF-beta 1 which is, in turn, required for inhibition of cytotoxicity and nephritogenicity. Our studies are consistent with TGF-beta 1 behaving, at least in some T cells, as a nonspecific final effector of clone-specific suppression.
 ...
PMID:Inhibition of murine nephritogenic effector T cells by a clone-specific suppressor factor. 796 56

In order to analyse the clonality of T cells in the inflammatory infiltrate of oral lichen planus (OLP), mucosal biopsies were obtained from seven patients with manifest disease. The biopsies were stained with MoAbs directed against 11 different T cell receptor (TCR) V-gene families, anti-CD4, anti-CD8 and IL-2 receptor (IL-2R). For comparison, the frequencies of the different TCR V-families were determined in biopsies from five patients with oral candidosis as well as in peripheral blood from three patients with OLP and from six healthy blood donors (HBD). The occurrence of the investigated TCR V-families varied between 0% and 7% in venous blood obtained from both HBD and OLP patients. T lymphocytes expressing the TCR V beta 3 and V alpha 2 in OLP biopsies were, however, detected in frequencies ranging between 18% and 40% of the total fraction of lymphocytes, a consistent finding for all the OLP infiltrates studied. The other nine TCR V-families examined appeared in low frequencies both in biopsies and in peripheral blood. V alpha 2+ and V beta 3+ cells were often localized adjacent to the basal membrane. In contrast, T cells in Candida-induced lesions did not express a biased TCR distribution, and most V-families studied appeared in frequencies of 0-6%. Thus, T lymphocytes in OLP lesions express a substantially higher frequency of TCR V alpha 2 and V beta 3 than expected from the distribution in blood. The clonal expansion of T cells observed in OLP suggests that a superantigen is involved in the pathogenesis of the disease. Whether this superantigen is of exogenous or endogenous origin needs to be investigated.
 ...
PMID:T cell receptor V-gene usage in oral lichen planus; increased frequency of T cell receptors expressing V alpha 2 and V beta 3. 799 13

Clonotype-positive (1B2+) T cells from 2C T cell receptor (TCR) transgenic mice were used to define the role of CD8 molecules in the induction phase vs. the effector phase of the primary response to class I alloantigens. Three main findings are reported. First, in the presence of exogenous lymphokines, resting CD8+ 2C cells gave strong proliferative responses to two alloantigens, Ld and Kbm11. In the absence of added lymphokines, however, CD8+ 2C cells responded only to Ld and not to Kbm11; Ld stimulated both interleukin 2 (IL-2) and IL-2 receptor (R) synthesis, whereas Kbm11 elicited only IL-2R synthesis. The primary response of CD8+ 2C cells was thus helper-independent (HI) to Ld but helper-dependent (HD) to Kbm11, presumably reflecting that Ld is a stronger antigen than Kbm11. Second, in contrast to CD8+ cells, CD8- 2C cells mounted only an HD and not an HI response to the strong Ld antigen; conversely, selecting for a minor subset of CD8hi cells enabled 2C cells to mount an HI response to the weak Kbm11 antigen. These findings, together with experiments with heterozygous vs. homozygous stimulator cells, suggest that HI and HD responses reflect differences in the overall avidity of T antigen presenting cell (APC) interaction: high-avidity interaction leads to strong intracellular signaling and an HI response, whereas low-avidity interaction causes weak signaling and an HD response; high-avidity T/APC interaction is heavily dependent on CD8 expression. Third, CD8 expression was found to be less important for CTL activity than for primary proliferative responses. Thus, in contrast to HI proliferative responses, CTL responses of 2C cells to Ld were CD8 independent. However, 2C lysis of Ld targets became strongly CD8 dependent in the presence of limiting doses of anti-TCR (1B2) antibody. Collectively, the data suggest that, both for T cell induction and the expression of effector function, CD8 molecules play a decisive role in augmenting TCR-mediated signaling, either by promoting TCR contact with antigen or delivering kinases (p56lck) to the TCR/CD3 complex, or both.
 ...
PMID:Resting and activated T cells display different requirements for CD8 molecules. 819 22

Binding of interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) stimulates Src family kinases, tyrosine phosphorylation of several proteins, conversion of Ras to its active GTP-bound form, and eventually c-fos, c-jun, and c-myc induction. The IL-2R beta chain plays a crucial role in IL-2R signaling. Within the cytoplasmic domain of the beta chain, a region essential for mitogenesis and another involved in binding the Src family kinase Lck have been defined. The beta chain itself is tyrosine-phosphorylated upon IL-2 stimulation. Since the adapter protein Shc acts upstream of Ras and is involved in T cell receptor-mediated Ras activation, we examined the role of Shc in IL-2 signaling. Shc was found to be tyrosine-phosphorylated upon IL-2 stimulation in CTLL-20 cells. After its phosphorylation, Shc interacted with another adapter protein, Grb2, and, via Grb2, with the Ras GTP/GDP exchange factor mSOS. After IL-2 stimulation, Shc also associated with the IL-2R beta chain. Thus, during IL-2 signaling, the interaction of Shc with the IL-2R beta chain and its simultaneous association with Grb2 and mSOS may couple IL-2R stimulation to Ras signaling.
 ...
PMID:The adapter protein Shc interacts with the interleukin-2 (IL-2) receptor upon IL-2 stimulation. 829 3

Beginning at the time of insulitis (7 wk of age), CD4+ and CD8+ mature thymocytes from nonobese diabetic (NOD) mice exhibit a proliferative unresponsiveness in vitro after T cell receptor (TCR) crosslinking. This unresponsiveness does not result from either insulitis or thymic involution and is long lasting, i.e., persists until diabetes onset (24 wk of age). We previously proposed that it represents a form of thymic T cell anergy that predisposes to diabetes onset. This hypothesis was tested in the present study by further investigating the mechanism responsible for NOD thymic T cell proliferative unresponsiveness and determining whether reversal of this unresponsiveness protects NOD mice from diabetes. Interleukin 4 (IL-4) secretion by thymocytes from > 7-wk-old NOD mice was virtually undetectable after treatment with either anti-TCR alpha/beta, anti-CD3, or Concanavalin A (Con A) compared with those by thymocytes from age- and sex-matched control BALB/c mice stimulated under identical conditions. NOD thymocytes stimulated by anti-TCR alpha/beta or anti-CD3 secreted less IL-2 than did similarly activated BALB/c thymocytes. However, since equivalent levels of IL-3 were secreted by Con A-activated NOD and BALB/c thymocytes, the unresponsiveness of NOD thymic T cells does not appear to be dependent on reduced IL-2 secretion. The surface density and dissociation constant of the high affinity IL-2 receptor of Con A-activated thymocytes from both strains are also similar. The patterns of unresponsiveness and lymphokine secretion seen in anti-TCR/CD3-activated NOD thymic T cells were also observed in activated NOD peripheral spleen T cells. Exogenous recombinant (r)IL-2 only partially reverses NOD thymocyte proliferative unresponsiveness to anti-CD3, and this is mediated by the inability of IL-2 to stimulate a complete IL-4 secretion response. In contrast, exogenous IL-4 reverses the unresponsiveness of both NOD thymic and peripheral T cells completely, and this is associated with the complete restoration of an IL-2 secretion response. Furthermore, the in vivo administration of rIL-4 to prediabetic NOD mice protects them from diabetes. Thus, the ability of rIL-4 to reverse completely the NOD thymic and peripheral T cell proliferative defect in vitro and protect against diabetes in vivo provides further support for a causal relationship between this T cell proliferative unresponsiveness and susceptibility to diabetes in NOD mice.
 ...
PMID:Interleukin 4 reverses T cell proliferative unresponsiveness and prevents the onset of diabetes in nonobese diabetic mice. 831 97

The association of rheumatoid arthritis (RA) with particular MHC class II genes suggests that autoantigen-specific T cell clones present in joints could be central to the pathogenesis of the disease. Previous investigations on the clonal diversity of T cells infiltrating the rheumatoid synovial membrane have yielded conflicting results. With the use of Southern blot analysis, we investigated the clonality of rheumatoid T cell lines expanded from peripheral blood, synovial fluid and synovial tissue. From peripheral blood lymphocyte (PBL) of RA patients and healthy normal controls, we also checked the consequences of two different culture conditions on the clonality of these cell lines. From control PBL, we found that in vitro non-specific expansion of non-clonal T cell populations does not create artefactual clonal selection. However, growing T cells in vitro with IL-2 seems to be able to lead to preferential expansion of cells bearing IL-2 receptor (IL-2R). We identified such in vivo activated IL-2-sensitive T cell clones frequently in RA synovial tissue (8/13) and more rarely in synovial fluid and peripheral blood (3/12). One patient presents the same T cell receptor gene rearrangements in synovial membrane of two affected joints. In RA synovial tissue, the frequency of these IL-2-responsive T cells is most prevalent among actively inflamed membranes removed early in the disease process. The role and the relevance to the disease of these IL-2-responsive T cells remain to be elucidated.
 ...
PMID:Clonality of T lymphocytes expanded with IL-2 from rheumatoid arthritis peripheral blood, synovial fluid and synovial membrane. 838 Mar 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>