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)

The aim of these experiments was to analyse the functional roles of phenotypically defined T cells from Buffalo strain rats with immunisation or neonatal thymectomy-induced autoimmune thyroiditis. Rats were depleted either of CD8-positive T cells by administration of the Ox8 monoclonal antibody or of activated T cells by administration of low-dose cyclosporin A (Cs A) with an anti-IL-2 receptor monoclonal antibody (ART-18), and the effects on subsequent disease assessed. Even though animals were not completely depleted of Ox8 cells, immunisation-induced thyroiditis was enhanced by Ox8 treatment, whereas thyroglobulin antibodies were reduced compared with controls. Subtherapeutic doses of either Cs A or ART-18 alone had little effect on thymectomy-induced thyroiditis, in contrast to Cs A and ART-18 in conjunction, which prevented disease developing. These results suggest important roles for CD8-positive and IL-2 receptor-bearing T cells in experimental autoimmune thyroiditis.
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PMID:The effect of T cell subset depletion on autoimmune thyroiditis in the Buffalo strain rat. 214 Aug 14

Thymocyte cell suspensions, prepared from mice at different ages, were cultured in vitro with human rIL-2. This stimulation resulted in a cell population that contained almost 50% TCR-gamma delta-positive cells if thymocytes were taken from fetal day 17 until just after birth. Analysis of the variable (V gamma) region used by the TCR-gamma delta cells revealed that 90% of them expressed TCR-V gamma 3, and less than 5% expressed TCR-V gamma 2. Cells positive for TCR-alpha beta were barely detectable. If fetal day 18 organ cultured thymus lobes, instead of a cell suspension, were stimulated with IL-2, no rise in the number of TCR-V gamma 3+ or TCR-delta+ cells was observed, whereas a partial outgrowth of TCR-alpha beta+ cells occurred. From day 1 after birth, the number of TCR-gamma delta cells recovered from an IL-2-stimulated thymocyte cell suspension dropped to reach a plateau of 15% of the total cell number, whereas TCR-V gamma 3+ cells became undetectable in older animals. TCR-alpha beta+ cells, on the other hand, quickly rose in cell number after birth. Kinetic analysis showed that the preferential outgrowth of TCR-V gamma 3+ cells in IL-2-stimulated fetal day 18 thymocyte cell suspensions was present from the onset of the culture; a significant proliferation of CD4 or CD8 single positive TCR-alpha beta cells was never observed. This lack of proliferation of TCR-alpha beta cells was not due to inhibition by the activated TCR-V gamma 3+ cells. Throughout the IL-2 culture, one-fourth of the TCR-V gamma 3+ thymocytes was positive for CD8. Analysis of the DNA content and the IL-2 receptor (IL-2R) p55 expression showed that during the first days of culture the TCR-V gamma 3+ cells had a much higher proliferation rate than the TCR-V gamma 3- cells, although TCR-V gamma 3+ IL2R p55+ cells could not be detected. From day 3 to 4 of culture, the proliferation rate of TCR-V gamma 3+ cells equaled that of the rest of the cells and less than 20% of the TCR-V gamma 3+ cells expressed the IL-2R p55. The biologic significance of our findings is discussed.
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PMID:Preferential proliferation of T cell receptor V gamma 3-positive cells in IL-2-stimulated fetal thymocytes. 214 32

Tumor infiltrating (TIL) and peripheral blood lymphocytes (PBL) were isolated from 18 patients with non-small cell lung cancer undergoing radical surgery. Surface marker analysis revealed that TILs and PBLs mainly consisted of CD3+ T cells and that TILs generally displayed a lower CD4/CD8 ratio. Differences were found in the expression of CD25 (IL-2 receptor) and DR (MHC class II) antigens, which were increased in TILs, and in the percentage of CD16+ natural killer (NK) cells, which was reduced in TILs as compared to PBLs. Accordingly, the NK activity of TILs was lower than that of PBLs, whereas neither TILs nor PBLs expressed spontaneous cytolytic activity against fresh autologous tumor cells, melanoma cells and the "NK-resistant" A549 lung carcinoma cell line. After 4 days of culture in medium with recombinant-interleukin-2 (rIL-2), TILs and PBLs acquired cytolytic activity against all cell targets, but TILs expressed higher levels of cytotoxicity than autologous PBLs only in 3 patients out of 16 tested. More importantly, both TILs and PBLs displayed similar levels of cytotoxic activity against autologous tumor cells. TILs and PBLs from 8 patients were also analyzed by a limiting dilution microculture system. Cloning efficiency was remarkably lower in TILs, and surface marker analysis of T cell clones confirmed that an accumulation of CD8+ lymphocytes, which displayed cytolytic activity in a lectin-dependent assay, occurred at the tumor site. The non-MHC-restricted cytolytic activity of TIL- and PBL-derived T cell clones against K562, A549, and allogeneic melanoma cells and the cytolytic activity against autologous tumor cells showed no significant differences. Only 53% of TIL clones released IL-2 in response to PHA + TPA stimulation, whereas 68% of PBL-derived clones were IL-2 producers. Moreover, most PBL- and TIL-derived clones released tumor necrosis factor alpha in response to mitogen stimulation.
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PMID:Peripheral blood and tumor infiltrating lymphocytes in non-small cell lung cancer: analysis at the population and clonal level. 217 60

Monoclonal antibodies to certain cell surface constituents on lymphocytes, monocytes and macrophages have been administered to Lewis rats with developing, established or adoptively transferred arthritis, to determine any immunomodulatory properties. Anti-CD4 antibodies against helper T-lymphocytes produced a dose related inhibition of developing arthritis; high dose levels completely suppressed all symptoms of arthritis and these rats were resistant to further attempts to induce arthritis. Anti-Ia (MHCII) antibodies also inhibited arthritis in a dose related manner; anti-pan T antibodies delayed the onset of arthritis, but antibodies against CD8 and IL-2 receptor positive cells were without effect. Development of type II collagen-induced arthritis was also inhibited by anti-CD4 treatment. Established arthritis could be temporarily inhibited by anti-CD4 antibodies, but rebound of arthritis invariably occurred after stopping treatment, as is the case with cyclosporin A. Similar results with anti-CD4 antibodies were obtained during treatment of arthritis adoptively transferred by arthritogenic T-lymphocytes. From these experiments it is clear that CD4 positive T-lymphocytes have a major role in the induction of adjuvant arthritis and that interaction between CD4 and Ia bearing cells is important. The rebound of arthritis that occurred after withdrawal of anti-CD4 treatment during established disease infers that cells in addition to helper T-lymphocytes are involved in the chronicity of arthritis, but these remain to be elucidated. These findings are discussed in relation to results with monoclonal antibodies in other models of arthritis and human rheumatoid arthritis; the prospects for human therapy are also discussed.
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PMID:Monoclonal antibodies and arthritis. 232 19

A subset of peripheral blood T lymphocytes coexpressing CD3 and IgG Fc receptors (FcR) (CD16/Leu-11 antigen) have been identified, isolated, and functionally characterized. The CD3+, CD16+ cells were established in short-term culture using growth medium containing interleukin 2 (IL-2). Both the freshly isolated cells and the cultured cell line stably expressed the CD3+, CD16+ phenotype. Furthermore, a majority of these T cells lacked either CD4 or CD8 expression. Like in vitro-activated cytotoxic T lymphocytes and natural killer (NK) cells, the CD3+, CD16+ cells showed numerous azurophilic granules. Although these cells failed to mediate significant levels of NK cell-mediated cytotoxicity even after stimulation with IL-2, they efficiently functioned as effectors of antibody-dependent cellular cytotoxicity (ADCC). The Ig isotype specificity of the ADCC was analyzed using an isotype switch-variant family of a murine anti-HLA monoclonal antibody (mAb). Similar to the CD3-, CD16+ NK cell population, the CD3+, CD16+ T cells preferentially used the IgG2a antibody to mediate ADCC. The CD3+, CD16+ cells demonstrated a proliferative response when cocultured with either a NK-sensitive tumor cell line, K562, or a NK-insensitive B lymphoblastoid cell line, CCRF-SB. The response against CCRF-SB was significantly inhibited by anti-IL-2 receptor antibody, whereas the response against K562 was only partially diminished. Cytotoxicity was also induced in the CD3+, CD16+ population by the presence of anti-CD3 mAb, indicating that cytotoxicity can be triggered by stimulation via the CD3-T cell antigen receptor complex. By isolating these CD3+, CD16+ cells from the peripheral blood of a normal, healthy individual, it has been possible to extensively study the morphology, antigenic phenotype, and functional behavior of this unique subset of T lymphocytes expressing IgG FcR.
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PMID:Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen). 241 63

Malignant cells of a patient with acute leukemia expressed hematopoietic stem cell antigens such as CD34 and HLA-class II but lacked lineage specific differentiation markers. The leukemic blasts differentiated into mature T cells within 14 days in the presence of a T cell conditioned medium or with a mixture of highly purified interleukin-2 (IL-2) plus recombinant interleukin-3 (IL-3) and recombinant granulocyte/macrophage colony-stimulating factor (GM-CSF). Phenotypically, the maturing cells acquired the T cell-specific differentiation antigens CD2, CD3, and CD8, whereas immature differentiation antigens such as CD34 and Leu19 as well as HLA-class II and the IL-2 receptor CD25 were concomitantly down-regulated within 14 days of in vitro culture. This in vitro maturation involved two to three synchronized cell divisions. Beyond 10 days of culture the leukemic cells produced mRNA specific for the T cell receptor beta and alpha chain, but at no time transcription of T cell receptor gamma chain-specific message was detectable. To our knowledge, these data represent the first in vitro model demonstrating the differentiation of phenotypically mature T cells from immature leukemic cells induced by the combined activities of IL-2 plus IL-3 and GM-CSF.
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PMID:Generation of mature CD3+ and T cell receptor (TCR) + T cells from a leukemic analogue of the putative human stem cell by T cell conditioned medium containing IL-3, IL-2, and GM-CSF. 245 58

Interleukin-2 (IL-2) responsiveness of Dermatophagoides farinae (Df)-stimulated lymphocytes from children with bronchial asthma was studied. Six-day culture of lymphocytes from allergic patients increased after an additional 3 days of incubation with recombinant IL-2. This phenomenon was not observed when the lymphocytes of patients allergic to Df were stimulated with ovalbumin (OVA). Normal lymphocytes stimulated with Df expressed Tac antigen (low-affinity IL-2 receptor) but, in contrast to the patients' lymphocytes, did not absorb nor respond to IL-2. Nonadherent responder cells cultured with Df-pulsed autologous adherent cells acquired IL-2 responsiveness, but those cultured with OVA-pulsed adherent cells did not. The monoclonal antibody to HLA-DQ framework (Leu 10 and clonab DQ), but not to HLA-DR framework (OKIa1) and HLA-DP (HLA-DP and clonab DP-DR), blocked the antigen-presenting cells from inducing IL-2 responsiveness. Nonadherent responder cells depleted of OKT4 (CD4)-positive cells failed to acquire IL-2 responsiveness, whereas depletion of OKT8 (CD8) cells had no impact. Taken as a whole, the results indicate that DQ-bearing adherent cells from allergic donors play a key role in presenting Df antigen to allergen-specific responder T cells, which are very likely to be members of the OKT4 positive subset.
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PMID:Allergen-specific induction of interleukin-2 (IL-2) responsiveness in lymphocytes from children with asthma. I. Antigen specificity and initial events of the induction. 247 92

In the course of a phase I trial, in which recombinant IL-2 (rIL-2) was infused intraperitoneally (i.p.) in patients with peritoneal carcinomatosis, we evaluated the effect on "tumor-associated lymphocytes" (TAL) isolated from the ascitic fluid. No major changes in the percentages of cells expressing the CD3, CD4, CD8, Leu-7, OKM1 and WT-31 antigens were detected either in TAL or in peripheral blood lymphocytes (PBL) after 7 days of rIL-2 infusion. In contrast the percentages of TAL (but not PBL) expressing surface IL-2 receptor (Tac), or LAK-1 antigen were sharply increased. Analysis of cytolytic functions showed a potentiation of the lytic activity against natural-killer (NK) sensitive K562 target cells and the de novo appearance of lytic activity against fresh melanoma cells. In one patient IFN-gamma was detected in the ascitic fluid following rIL-2 infusion. T-cell clones derived from the patient were analyzed for the IFN-gamma production. While only approximately 40% of PB-derived control clones produced medium to low amounts of IFN-gamma, all of the TAL-derived clones produced medium to high amounts of the lymphokine.
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PMID:Phenotypic and functional characteristics of tumor-associated lymphocytes in patients with malignant ascites receiving intraperitoneal infusions of recombinant interleukin-2 (rIL-2). 249 78

Reactivity of murine thymocytes with the Dolichos bifloris agglutinin (DBA) was examined using flow cytometry. This agglutinin, which has nominal specificity for alpha-linked N-acetyl-D-galactosamine residues, labels 1-4% of unfractionated BALB/c thymocytes. Among thymocyte subpopulations identified on the basis of CD4/CD8 labeling, DBA bound to a substantial percentage of the CD4-8- thymocyte subpopulation. In addition, small populations of thymocytes expressing CD4 and/or CD8 were also labeled with DBA, but with less intensity then seen on many CD4-8- cells. Within the CD4-8- thymocyte population, labeling with DBA was positively correlated with reactivity with J11d antibody, the expression of IL-2 receptor and high levels of the homing receptor molecule, MEL-14. Reactivity with DBA was negatively correlated with the expression of Lyt-1, V beta 8 TCR determinants, and CD3.
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PMID:Characterization of murine thymocyte subpopulations reacting with Dolichos bifloris agglutinin. 249 86

Lymphocytes, co-expressing CD4/Leu7 and CD8/Leu7 markers respectively, taken from two patients having large granular lymphocytosis taking an indolent clinical course have been comparatively studied for function as NK cells and T cells. Both large granular lymphocytes (LGLs) were acid phosphatase positive and showed a beta-glucuronidase reaction in their cytoplasmic granules. Studies on case 1 indicated that the CD4/Leu7 lymphocytosis with LGL morphology takes a benign clinical course with mild neutropenia as well as those of CD8/Leu7 LG lymphocytosis. Both CD4/Leu7 and CD8/Leu7 LGLs behave similarly in their lack of NK activity, and manifest decreased IL-2 production in vitro and show a low IL-2 receptor expression unrelated to their T cell phenotype, but behave differently in influencing the immunoglobulin production in vitro and the ADCC activity, depending on their T cell phenotype and on the expression of Fc receptor, respectively. Furthermore, the altered Fc receptors which were undetectable by the Leul 1 antibody but were still effective for ADCC activity might be present in case 2 LGLs.
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PMID:CD4/Leu7 and CD8/Leu7 large granular lymphocytosis: comparative studies between NK cells and T cells. 251 16


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