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)

Several studies have reported a suppressed immune function (e.g. blast transformation) during depression. In an attempt to define the cellular basis of the reported immune disorders, the present study investigates the leukocyte cell subset profile of minor, simple major, and melancholic depressives, versus normal controls. We have counted the number of white blood cells (WBC) lymphocytes, monocytes, and granulocytes, while the number of lymphocyte (sub)populations has been identified by phenotype, using monoclonal antibody staining in conjunction with flow cytometry. The following cell surface antigens were determined: CD3+ (pan T), CD19+ (pan B), CD4+ (T helper/inducer), CD8+ (T suppressor/cytotoxic), CD4+CD45RA (T-memory cells), CD4+CD45RA+ (T-virgin cells), surface Ig, class II MHC HLA-DR, and CD25+ (IL-2 receptor). By means of pattern recognition methods, we established distinct immunological changes in minor and simple major depressed and in melancholic patients, setting them apart from the reference population. Depression, per se, is characterized by a higher number of WBC, monocytes, class II MHC HLA-DR, and memory T cells. Minor and simple major depressives exhibited an increased T helper/suppressor ratio. Increased numbers of IL-2 receptor bearing cells are a hallmark for major depression. Melancholics showed an increased number of pan T, pan B and T suppressor/cytotoxic cells. It was concluded that the established immune cell profile of depressed patients may point towards the existence of a systemic immune activation during that illness.
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PMID:Evidence for a systemic immune activation during depression: results of leukocyte enumeration by flow cytometry in conjunction with monoclonal antibody staining. 157 66

To assess the role of T lymphocytes in the initiation of the allergic asthmatic response we have investigated T-cells subsets and their activation markers in bronchoalveolar lavage (BAL) fluid recovered 10 min after local challenge of the bronchial mucosa with allergen or saline. Endobronchial challenge was performed in 13 mildly atopic asthmatic patients (FEV1% predicted range, 78.2 to 116.5) and 10 normal volunteers. In all of the asthmatics but in none of the normal subjects allergen but not saline exposure resulted in visible bronchoconstriction. Analysis of BAL by flow cytometry showed no differences in the overall number of T cells (CD3+) and their CD4+ and CD8+ subsets per milliliter of BAL between the groups of normal subjects and asthmatics. However, within 10 min of allergen challenge, in the asthmatics but not in the normal subjects, there occurred a significant loss of CD3+ cells (p less than 0.01) comprising mostly CD4+ (p less than 0.05) but also CD8+ cells, with a consequent decrease in the CD4:CD8 ratio. At this early time point no differences in the extent of expression of the T-cell activation markers, IL-2 receptor, and HLA-DR were found. These results provide evidence to support a role of T lymphocytes early in the allergen-induced inflammatory response in asthma.
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PMID:Early changes in T lymphocytes recovered by bronchoalveolar lavage after local allergen challenge of asthmatic airways. 159 88

We tried a infusion of interleukin-2 (IL-2) of a relatively low dose via an intrasplenic arterial catheter connected to a chronometric infusion (IS-IL-2). Eighteen patients of colorectal cancer with metastases to the liver or lung or of unresectable hepatoma received a 24 hour continuous infusion with low dose recombinant of IL-2 (mainly 8 x 10(5) JRU/day) for 25-40 days. All patients tolerated this protocol of the therapy and the main toxic effects were fever and general fatigue. Such serious toxicity as previously reported by high dose IL-2 therapy was not observed. Data of hepatic and renal functions were normal. IS-IL-2 therapy induced a high incidence of eosinophilia (12/18) and thrombocythemia (12/18). Peripheral natural killer (NK) and LAK activities were augmented in all patients and total white blood cell counts were increased during IS-IL-2 therapy. An increase in IL-2 receptor expression of peripheral blood mononuclear cells and significant rises in numbers of Leu11 (CD16)+, OKM1(CD11)+ and OKIa1(HLA-DR)+ were observed. Of 18 patients 12 were evaluable for their response to therapy. Partial response (PR) was observed in one unresectable hepatoma and 11 demonstrated no change (NC) or progressive disease (PD). Six patients were not evaluable because of additional therapy (3 cases) or decreasing tumor cell markers having no measurable lesions (3 cases). Three patients of colorectal cancer from an unresectable group were presumed to have micrometastases to the liver as suggested by an elevated serum CEA level. After receiving IS-IL-2 therapy they demonstrated a decrease in the serum CEA level for more than 3 years after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical trials of intrasplenic arterial infusion of interleukin-2 (IS-IL-2) to patients with advanced cancer. 162 39

Regulation of the induction of suppressive activity in peripheral blood mononuclear cells (PBMC) by human major histocompatibility complex (MHC) class II+ CD4+ CD45R+ suppressor-inducer T-cell clones has been investigated. Previously, it was shown that in this system, cyclosporin A-sensitive precursors gave rise to allo-indifferent MHC-unrestricted CD4+ suppressive cells. Their induction could be blocked by monoclonal antibodies (mAb) to multilocus MHC class II gene products (TU 39) but not by mAb preferentially reacting with HLA-DR, -DQ or -DP molecules. This product, functionally defined, was termed 'DY'. It is shown here that induction of suppression by DY follows established activation pathways: (i) cell adhesion was required because CD11a (LFA-1) mAb blocked suppressor-induction; (ii) CD4 mAb also blocked, consistent with the involvement of class II products in suppressor-induction; (iii) cell proliferation was required because mAb to transferrin receptors, or irradiation, inhibited induction; and (iv) such proliferation appeared to be interleukin (IL)-2-dependent because it was blocked by mAb to IL-2 receptor, and enhanced by exogenous IL-2 but not IL-4. It was also enhanced by exogenous IL-1 and IL-6, but not by IL-3, tumour necrosis factor-alpha (TNF alpha) or interferon-gamma (IFN-gamma). It therefore seems that the requirements for activation of suppression by CD4+ DY+ T-cell clones in this in vitro model bear many similarities to those for CD4+ helper T cells, namely, mediation by MHC class II with CD4 involvement, dependency on LFA-1-influenced cell interactions, and reliance on clonal expansion caused by IL-2 and possibly amplified by IL-1 and/or IL-6.
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PMID:CD4+ CD45R- suppressor-inducer T-cell clones: requirements for cellular interaction, proliferation and lymphokines for the induction of suppression in peripheral blood mononuclear cells. 169 2

The purpose of this study was to elucidate a possible immune response to tumor cells mediated by tumor-infiltrating lymphocytes (TIL) in lung cancer. In flow cytometry, the majority of T-cells of TIL were CD45RA-, CD45RO+, and CDw29high, and expressed HLA-DR. The expression of interleukin 2 receptor beta chain increased in both CD4+ and CD8+ TIL compared with both types of T-cells in peripheral blood. These results indicate that the major population of TIL is activated memory T-cells. The TIL preparation, which was usually contaminated with 5 to 10% tumor cells, did not exhibit any response in autologous mixed lymphocyte-tumor culture even in the presence of interleukin 2 (IL-2) in all five cases tested. Although purified T-cells from TIL showed the positive response in only 1 of 10 cases tested without addition of IL-2, it occurred in 7 of 10 cases in the addition of a low concentration of IL-2. The IL-2-dependent response to irradiated autologous tumor cells was suppressed when nonirradiated autologous tumor cells were added to the culture. Culture supernatants of four lung cancer cell lines and freshly prepared lung cancer cells obtained from 6 cases exhibited suppressive activity against anti-CD3 antibody-induced mitogenesis of peripheral blood mononuclear cells from healthy donors. We suggest that, taken together, (a) the major population of TIL in lung cancer are activated memory T-cells, and they include tumor-reactive ones, and that (b) the function of the TIL is impaired by unavailability of IL-2 and/or by suppression due to lung cancer cell-derived factor(s).
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PMID:Tumor-reactive T-cells accumulate in lung cancer tissues but fail to respond due to tumor cell-derived factor. 173 36

The evaluation of activation markers such as T4/T8 ratio and HLA-DR expression of lymphocytes of bronchoalveolar lavage (L-BAL) is an important clinical approach for the staging of sarcoidosis. However, it is not known to what extent this is paralleled by an exaggerated lymphocyte function. We investigated the dependence of L-BAL activation markers on the production of interleukin-2 (IL-2) by L-BAL and on the soluble IL-2 receptor serum level (sIL-2R) in 116 patients with sarcoidosis. In none of the combinations tested was a correlation between the two groups of parameters found; r less than 0.5, upper 90% confidence limit of r less than 0.8. Interestingly, IL-2 production is independent of HLA-DR+ T4 L-BAL, and sIL-2R production is independent of the percentage of IL-2+ L-BAL. Our data indicate that the L-BAL activation markers and the functional activity of T-cells represent independent phenomena.
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PMID:Correlation of clinical and immunologic parameters of the inflammatory activity of pulmonary sarcoidosis. 174 45

Nickel is the major cause of metal-induced allergic dermatitis. Twelve nickel-specific T cell clones were used to investigate the cellular immune reactions occurring in nickel sensitivity. The selection between the alternative T cell receptors alpha beta and gamma delta and two alternative V beta genes (V beta 5 and V beta 8) were studied to see if nickel induces a selective pressure for clones bearing particular genes. Cell surface markers were studied by monoclonal antibodies and flow cytometry. Soluble mediators were measured by an ELISA method. The clones used T cell receptor alpha beta genes but did not use V beta 5 or V beta 8. They were T helper clones with a primed memory marker (CD3+ CD4+ CD8- CD45RO+) and carried HLA-DR. None of the clones secreted IL-1 alpha, all of them secreted IL-2 receptor. Four clones secreted IL-1 beta, six IL-4 and seven IL-6, the peaks in IL-2R and IL-6 secretion preceding IL-4 secretion. The clones helped immunoglobulin synthesis. The clones from late effector phase of the nickel allergic reaction favours the use of T cell receptors alpha beta genes. Nickel-specific clones were phenotypically indistinguishable but differed in soluble mediators produced.
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PMID:Characterization of nickel-specific T cell clones. 182 95

Significant proliferative responses of peripheral blood mononuclear cells (PBMC) to crude Plasmodium falciparum schizont antigen (M.Ag) or purified recombinant 31.1 Ag (part of gp 195) were observed only in 46 and 39%, respectively, of 50 healthy subjects 5 to 63 years old living in Gabon, a malaria-endemic area. High responses to pokeweed mitogen were observed in all the subjects except one. Interferon-gamma (IFN-gamma) production paralleled the proliferative response, but in some subjects proliferation without a IFN-gamma response was observed. The proportion of subjects responding to M.Ag and 31.1 Ag increased with age. By cytofluorometric analysis performed with PBMC from 27 subjects, a substantial proportion of CD3+ T cells was found to bear the activation marker HLA-DR. However, the CD3+ cells expressed very low levels of CD25 (p55 chain of IL-2 receptor). The expression of CD25 on T cells and their capacity to respond to M.Ag were significantly correlated. In four subjects an increase in the percentage of CD3+ cells bearing the very late activation marker VLA-1 was observed.
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PMID:In vivo decreased expression of CD25 (p55 chain of IL-2 receptor) on CD3+ T cells correlates with low in vitro responsiveness to Plasmodium falciparum antigen in subjects living in a malaria endemic area. 182 93

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

Lymphocyte clones were isolated from CD4+ peripheral-blood lymphocytes (PBL) of melanoma (Me) patient 9923 (HLA-DR7, DQw2, w6), co-cultured for 30 days with autologous accessory cells, allogeneic Me (Me 1811) (HLA-DR7, DQw1, w2), IL-1 beta (2 U/ml) and IL-2 (15 IU/ml). The 55 clones tested displayed a CD3+, CD4+, CD8-, T-cell receptor (TCR) alpha/beta+, gamma/delta- phenotype. Twenty clones were assayed for proliferation in the presence of Me 1811 and B-lymphoblastoid cell line (LCL) 1811, both expressing HLA-class-I and -II (DR7 and DQw2 shared with patient 9923), intercellular adhesion molecule-1 (ICAM-1) and lymphocyte-function-associated antigen-3 (LFA-3) molecules. Eight clones were found to be reactive to Me 1811 but not to LCL 1811. Specificity analysis of these 8 clones revealed that each of them proliferated only to Me 1811, not to other 14 Me and 12 different LCL, suggesting recognition of melanoma-associated antigen (MAA) expressed on the stimulating Me. One clone (103) was analyzed in more detail. A wider specificity analysis showed that it reacted to Me 1811 but not to 10 other Me expressing or not HLA-DR7, 5 normal melanocyte cultures (2 of them typing HLA-DR7-positive when exposed to interferon-gamma--IFN-gamma), 4 tumors other than Me and 20 different LCL. Clones did not show proliferation in the presence of autologous Me cells. Clone proliferation in response to Me 1811 was significantly inhibited by monoclonal antibodies (MAbs) directed to CD3, TCR alpha/beta, TCR beta chain V12, CD4 and HLA-DR. Moreover, following stimulation with Me 1811, clone 103 showed increased surface expression of CD25 (IL-2 receptor) and CD71 (transferrin receptor) and produced significant amounts of IL-2 and IFN-gamma. The supernatant taken from co-culture of clone 103 with Me 1811 augmented the cytotoxicity of PBL 9923 and other allogeneic PBL against K562 and Me 1811. Thus, the lymphocyte clone 103 is a CD4+ Th clone which uses its CD3/TCR alpha/beta complex to recognize an MAA in conjunction with HLA-DR7. Availability of this type of reagent may prove useful to identify and characterize MAA recognized by T lymphocytes.
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PMID:Human allogeneic melanoma-reactive T-helper lymphocyte clones: functional analysis of lymphocyte-melanoma interactions. 183 14


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