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)

Induction of suppressor cells has been hypothesized to explain the variability in the efficacy of Mycobacterium bovis BCG vaccination against mycobacterial diseases. In this study, we induced suppressor T cells by in vitro stimulation of peripheral blood mononuclear cells obtained from BCG-vaccinated healthy subjects. These suppressor T cells were CD4+ and did not affect interleukin-1 production by adherent cells in response to BCG. However, they suppressed interleukin-2 (IL-2) production and IL-2 receptor expression by the responding cells. Exogenous addition of IL-2 could partially restore the responsiveness of the indicator cells. To further characterize the cells responsible for suppression, T cell clones were established by limiting dilution. All the established T cell clones expressed CD4 marker, proliferated in response to BCG, were cytotoxic for antigen-presenting cells, and suppressed the antigen-induced proliferation of the indicator cells. Both suppression and cytotoxicity were not mediated by soluble factors but required cell-to-cell contact and were HLA-class II restricted. These results suggest that preferential killing of antigen-presenting cells by CD4+ T cells may be responsible for in vitro observed suppression in our system.
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PMID:Mycobacterium bovis BCG-induced Th1 type CD4+ suppressor T cells act by suppressing IL-2 production and IL-2 receptor expression. 874 54

R24 is a monoclonal antibody directed against the cell surface ganglioside GD3. It can detect GD3 on the surface of a subset of T lymphocytes and can stimulate proliferation and secretion of cytokines in vitro. In the present report, we examined the effects of the R24 antibody upon antigen-specific T cell response, employing an HLA-DR7-specific T cell clonal model. As previously shown, primary stimulation of HLA-DR7-specific alloreactive T cell clones by transfectants expressing HLA-DR7 alone (t-DR7) in the absence of B7 co-stimulation resulted in anergy. Binding of cell surface GD3 on HLA-DR7-specific alloreactive T cell clones with R24 under these anergizing conditions resulted in interleukin-2 (IL-2) accumulation and prevented the induction of alloantigen-specific T cell clonal anergy. Binding of GD3 by R24 also prevented anergy under conditions where B7:CD28 interactions were blocked by CTLA4-Ig. The effect of R24 was abrogated in the presence of a combination of monoclonal antibodies for the alpha and beta chains of the IL-2 receptor (IL-2R) or a neutralizing anti-IL-2 antibody. R24 does not appear to interact directly with the IL-2R since incubation of T cell clones with R24 did not induce early activation of IL-2R associated Jak kinases, Jak1 and Jak3, as was induced following incubation with IL-2. In contrast, incubation of HLA-DR7-specific clones with t-DR7 in the presence of R24 did result in phosphorylation of IL-2R related Jak kinases after 24 h. Our data indicate that the membrane ganglioside GD3 structure recognized by R24 may play an important role in antigen-specific T cell clonal response.
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PMID:R24 anti-GD3 ganglioside antibody can induce costimulation and prevent the induction of alloantigen-specific T cell clonal anergy. 881 60

The aim of this study was to quantify and characterize the CD4+ and CD8+, CD45RA+, CD45RO- T-lymphocytes that paradoxically expressed the CD29 bright+ phenotype in health and in rheumatoid arthritis. We further evaluated their clinical implications. Blood samples were obtained from 100 patients with rheumatoid arthritis and 40 age- and sex-matched controls. Cell surface antigens and interleukin-2 (IL-2) binding were detected on CD4+ and CD8+ peripheral blood T-lymphocytes (T-PBL) by three-colour flow cytometry. One-third of the patients were clinically evaluated at the time of blood sampling. In healthy donors, we found 16 +/- 14% of CD29 bright+ cells among CD4+, CD45RA+, RO- T-PBL. These "false naive" CD4+ T-PBL were Leu-8+, and a majority expressed the CD25/p55 receptor (IL-2R alpha chain), while a minority showed the CD11a bright+, CD69+ and/or CD122/p75+ (IL-2R beta chain) phenotype, and few cells were CD31 bright+ and HLA-DR+. In rheumatoid arthritis, their proportion among CD4+, CD45RA+, RO- cells increased to 25 +/- 15% (P < 0.001, compared with controls). In patients, the reductions in CD31 and CD38 expression (P < 0.05 for both), as well as the enhanced CD25 expression (P < 0.001) on CD4+, CD45RA+, RO- T-PBL reflected a more differentiated phenotype. The occurrences of CD25 and CD122 were increased on false naive CD4+ T-PBL (0.01 < P < 0.001); however, the binding of IL-2 remained very low (in contrast to the binding of IL-2 on CD45RO+ T-PBL). Furthermore, a major subset of CD8+, CD45RA+, RO- T-PBL (45 +/- 17% in controls) expressed the CD29 bright+ phenotype. These "false naive" CD8+ T-PBL included a great many of CD11b+, CD28- cells, while a minority showed the HLA-DR+, CD69+ and/or CD122+ phenotypes. Patients with low levels of IgM rheumatoid factors (IgM-RF; but with active disease) had an elevated proportion of CD45RA+, RO- cells among the CD8+ T-PBL, in part due to an increased proportion of false naive cells (P < 0.05). In patients, the false naive CD8+ T-PBL showed down-regulated CD11b and an increased expression of IL-2 receptor chains (CD25 and CD122; 0.05 < P < 0.01), but without a significant increase in IL-2 binding. More CD69 on false naive CD8+ T-PBL was found in patients with high levels of IgM-RF (P < 0.005 compared to patients with low IgM-RF). Finally, both false naive CD4+ and CD8+ T-PBL correlated with the clinical process and outcome variables (0.05 < P < 0.01). The levels of activated false naive (CD4+ T-PBL (CD25+ and/or CD122+) or CD8+ T-PBL (CD69+ and/or CD122+) were associated with clinical parameters of disease activity (0.05 < P < 0.01). Thus, in rheumatoid arthritis, false naive T-PBL showed important qualitative differences. The levels of activated false naive T-PBL could be particularly interesting for monitoring disease evolution.
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PMID:Flow cytometric characterisation of the "false naive" (CD45RA+, CD45RO-, CD29 bright+) peripheral blood T-lymphocytes in health and in rheumatoid arthritis. 885 29

Ulcerative colitis (UC) is a disease of acute on chronic at the active stage when lymphocytes, plasma cells as well as neutrophils and eosinophils infiltrate in the colonic mucosa. Molecular pathoimmunology of UC was discussed in this article from the viewpoint of disease susceptibility gene, immune activation gene of immunocompetent cells, molecular biology of cytokines, and molecular biology of colonic epithelial cells. HLA-DR2, DRB1* 1502, is the most susceptive gene for development and intractability of Japanese UC, and HLA-BW52 which was most frequently associated with Japanese UC and HLA-B35 which was also associated with Jewish UC were reported to have a common origin. Expression of IL-2 receptor and HLA-DR protein used as immune activation genes of lymphocytes was accelerated in UC. Overexpression of proinflammatory cytokines such as IL-1, IL-6 and IL-8 was found in the colonic mononuclear cells of UC, but IL-2 mRNA expression was not accelerated in UC. Therefore, immunological imbalance in the colonic mucosa may play an important role in the pathophysiology of UC.
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PMID:[Molecular pathoimmunology of ulcerative colitis]. 892 Jun 92

The paper is a review of the literature on cellular and humoral immunity in schizophrenic patients. The reports have revealed that there are manifestations of autoimmunological process in a subgroup of schizophrenics (among others: increased serum level of specific and non-specific autoantibodies, decreased lymphocyte interleukin-2 production, increased soluble IL-2 receptor concentration, increased serum IL-6 level, presence of lymphocyte abnormalities and association with HLA antigens. It is suggested that virus infection may provoke the appearance of autoimmunological reaction, while genetic factors might increase some predisposition to this reaction. The reports have also revealed that autoimmunity may play a role in pathogenesis of schizophrenia in a subgroup of schizophrenic patients who have immunological abnormalities.
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PMID:[Changes of humoral and cellular immunity in schizophrenia]. 898 18

The immune response in liver cirrhosis and hepatocellular carcinoma is receiving renewed attention in consideration of the possible treatment with biological response modifiers. The aim of this study was to evaluate whether cirrhosis and hepatocellular carcinoma induce any modification in peripheral lymphocyte subsets. Lymphocytes were evaluated (number/percentage) in 61 patients with hepatocellular carcinoma, 35 with cirrhosis and 24 healthy controls. Using flow cytometry, 10 lymphocyte subpopulations were assayed, plus the CD4/CD8 ratio. Results demonstrated no change in the number of lymphocytes; cirrhosis and hepatocellular carcinoma patients had significantly more HLA-DR+ (p = 0.001) and CD3+/HLA-DR+ (activated T) (p = 0.002) and fewer CD3+ (mature T) (p = 0.02) cell than controls; hepatocellular carcinoma patients had significantly more CD3+/CD56+/CD16- (cytotoxic non-MHC restricted T cells) and CD25+ (IL-2 receptor positive cells). If the percentages of all cells with cytotoxic-T activity were pooled, a significant increase (p = 0.03) was seen in hepatocellular carcinoma patients. In conclusion, in contrast to previous data, hepatocellular carcinoma patients reveal an increased number of cytotoxic non-MHC restricted T cells.
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PMID:Activation of cytotoxic and natural killer T-cell system in patients with hepatocellular carcinoma and cirrhosis. 913 93

The function and phenotypes of CD4+ lymphocytes in infants are different than in adults and are modulated by maturational changes and exposure to environmental antigens. Infants of non-human immunodeficiency virus (HIV)-infected mothers and uninfected infants of HIV-infected mothers, 0 to 6 months of age, were examined for CD4+ lymphocyte function by in vitro interleukin-2 (IL-2) production and for CD4+ phenotypes by three-color flow cytometry. A minority of these uninfected infants (28%) had functional responses similar to those of healthy adult women (IL-2 production in response to anti-CD3, alloantigen, and mitogen), while the remainder were capable of responding to alloantigen and mitogen but not to anti-CD3. We did demonstrate reduced phytohemagglutinin-stimulated IL-2 production in uninfected infants born to HIV-seropositive mothers compared to that in infants from seronegative mothers. The proportions of CD3+ CD4+, CD4+ HLA-DR- CD38+, and CD4+ CD45RA+ RO- (naive) lymphocytes were much higher in infants than in adults, and the proportions of CD4+ CD45RA- RO+ (memory) and CD4+ CD25+ (IL-2 receptor-bearing) lymphocytes were lower in infants than in adults. The proportions of activated (CD4+ HLA-DR+ CD38+) and memory (CD4+ CD45RA- RO+) lymphocytes were increased in uninfected infants of HIV-infected mothers compared to infants of uninfected mothers. Therefore, T-helper-cell function is immature in many infants, but the CD4+ lymphocytes of some HIV-exposed, uninfected infants have been stimulated by antigen at an early age.
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PMID:Function and phenotype of immature CD4+ lymphocytes in healthy infants and early lymphocyte activation in uninfected infants of human immunodeficiency virus-infected mothers. 914 77

Peripheral blood lymphocytes from healthy women were studied during pregnancy and postnatally, and were compared with lymphocytes from an age-matched non-pregnant control group. Compared with non-pregnant women, the total white cell count was significantly increased at all pregnancies and also post-partum. In pregnancy the absolute number and percentage of T lymphocytes was slightly elevated while almost no changes in B cells were found. No significant changes were found in the percentage of suppressor/cytotoxic (CD8+), of helper/inducer (CD4+) T lymphocytes, nor of CD4+/CD8+ ratio at any stage of pregnancy and puerperium. The most remarkable changes of the immune system occurred in the group of HLA-DR+ and CD56+ activated T cells. The cell numbers showed a significant increase in the first trimester (< 14 weeks) and decreased slightly from stage to stage. Lower values in NK (natural killer) cells and higher levels of IL-2 receptor positive T lymphocytes did not reach significant levels of change.
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PMID:Changes in lymphocyte subsets during normal pregnancy. 948 64

Accumulating evidence indicates that alloreactive donor T cells confer both graft-versus-host (GVH) and graft-versus-leukaemia (GVL) reactivity following allogeneic bone marrow transplantation. We have developed a method to deplete alloreactive donor T cells with an immunotoxin targeting the alpha chain of the IL-2 receptor. In patients with chronic myeloid leukaemia and their HLA-identical sibling donors, we measured donor helper T-lymphocyte precursor frequencies (HTLPf) against recipient peripheral blood mononuclear cells (PBMNC; donor versus host), recipient leukaemia cells (donor versus leukaemia) and third-party PBMNC, before and after the depletion. In seven pairs there was a 4.3-fold reduction of donor-versus-host HTLPf (P=0.017), without a significant change in the donor frequencies against third party (P=0.96). In eight further donor-recipient pairs, immunotoxin-depleted donor versus patient PBMNC HTLPf 4.5-fold (mean 1/155,000 before and 1/839,000 after depletion, P=0.007). There was a smaller non-significant 1.8-fold reduction in donor-versus-leukaemia HTLPf from 1/192,000 to 1/334,000 (P=0.19). These results suggest that selective T-cell depletion can significantly deplete donor anti-host reactivity while conserving anti-leukaemia reactivity in HLA-matched donor-recipient pairs.
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PMID:Specific depletion of alloreactive T cells in HLA-identical siblings: a method for separating graft-versus-host and graft-versus-leukaemia reactions. 963 3

Transient immunodepression appears a few hours after surgery and usually regresses spontaneously within 15-20 days. In this study, cellular and humoral immunity parameter values were compared prior to and 24 h, 7 days and 14 days after laparotomic and laparoscopic cholecystectomy (12 patients and 25 patients respectively) operated at the University of Turin's First Surgical Clinic, to look for differences in the immunological effects of these two types of surgery. The following parameters were determined: IgG, IgA, IgM, C3, C4, granulocytes (CD11c), lymphocytes, B lymphocytes (CD19, CD19-CD15), T lymphocytes (CD3), T helper cells (CD3-CD4), T suppressor cells (CD3-CD8), CD4/CD8 ratio, NK cells (CD16), monocytes (CD14, CD11c-CD14), IL-2 receptor expression (CD25), HLA-DR expression (total HLA-DR, HLA-CD3), total cytotoxic activity (CD57), T cell cytotoxic activity (CD8-CD57), and NK cell cytotoxic activity (CD16-CD57). Granulocytes increased significantly (p < 0.05) in both groups. The increase was more marked in the laparotomy group and still evident on the 7th and 14th days. Total T cells, T helpers and NK cells fell after 24 h (p < 0.05) in this group only. These results suggest that laparoscopy is associated with less substantial immunological changes than laparotomy.
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PMID:[Transient immunosuppression after abdominal surgical intervention]. 965 96


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