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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several immunological functions of B and T cells including IL-2 receptor expression on T cells were measured in 12-month-old Fisher-344 male rats maintained from 6 weeks of age on an ad libitum (AL) or a 40% food-restricted (FR) diet. Direct anti-SRBC plaque-forming cell (PFC) assays revealed a higher response in FR rats than in AL rats when splenocytes were cultured with or without recombinant interleukin-2 (rIL-2). B cell functions were studied by using nylon wool-purified splenic B cells stimulated either with rIL-2, lipopolysaccharide (LPS), or Salmonella typhimurium mitogen (STM) as a thymus-independent antigen. Reserve plaque assay showed no difference between FR and AL rats in the secretion of anti-IgM and anti-IgG antibodies. In addition, no difference was found in proliferation of B cells stimulated by LPS, STM mitogens or rIL-2. Although purified splenic T cells demonstrated an equally proliferative response in FR and AL rats when cultured with concanavalin A (Con A) or phytohemagglutinin (PHA), T cells in FR rats developed higher responses when stimulated with an alloantigen and rIL-2. Time-course studies carried out to measure high-affinity (HA) IL-2 receptor (R) molecules by using purified T cells with rIL-2 and 125I-labeled IL-2 revealed a higher expression of IL-2R molecules on T cells of FR rats than on T cells of AL rats at 72 h after culturing with Con A.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunological functions in food-restricted rats: enhanced expression of high-affinity interleukin-2 receptors on splenic T cells. 253 90

The activation state of thymic T and B lymphocytes was phenotypically and functionally explored in patients with Myasthenia Gravis (MG). We detected no phenotypic signs of activation in fresh total thymic lymphocyte suspensions (CD25 expression) while functional signs of activation were reflected by a significantly higher sensitivity to recombinant IL-2 (rIL-2) without any previous stimulation in MG patients as compared to controls. The response to rIL-2 was time-and dose-dependent, was inhibited by a blocking anti-IL-2 receptor antibody, and was associated to an increase of CD25+ T cells. Thymic B-cell populations purified after T cell and macrophage depletion, expressed at variable levels activation markers such as the transferrin receptor, the CD25, 4F2, CD23 and B8.7 Ag, indicating that a marked proportion of them are activated. Moreover, these B-cell populations were spontaneously sensitive to BCGF-12-kD and to a lesser extent to rIL-2, demonstrating that they also exhibit functional signs of activation. The largest proportion of activated B cells and the most intense response to BCGF-12-kD was found in patients presenting the highest anti-acetylcholine receptor (AChR) titers. Our data confirm the hyperactivity of the thymus gland in MG, reflected by the presence of T and B cells with functional signs of pre-activation. These cells could conceivably be located in lymphoid follicles and may represent autoreactive cells involved in the autoimmune process. Whether they are sensitized to AChR remains to be investigated.
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PMID:B- and T-cell activation in the thymus of patients with myasthenia gravis. 262 39

Myasthenia Gravis (MG) is an autoimmune disorder of neuromuscular transmission associated with antibodies (Ab) against acetylcholine receptor (AChR). Autoantibody production is a T-cell-dependent phenomenon perhaps caused by aberrant immunoregulation. So far, a possible role for immunoregulatory molecules has not been investigated in the pathogenesis of MG. Since interleukin-2 (IL-2) is able to induce peripheral blood mononuclear cell (PBMC) proliferation without a previous activating signal and to upregulate IL-2-receptor expression, we have evaluated the activation state of PBMC in patients with MG, by cytofluorographic analysis of CD25 expression and by testing their sensitivity to recombinant IL-2 (rIL-2) without any known previous stimulation. We found no significant difference in CD25 expression in a large group of patients compared to controls. However, proliferative responses to rIL-2 were significantly higher in MG patients than in controls. In MG, as in controls, this response was time- and dose-dependent, was inhibited by an anti-IL-2 receptor Ab and correlated with an increased percentage of CD25+ T cells after rIL-2 exposure. The response was greater in patients with a high anti-AChR Ab titer and a severe form of the disease, and in patients tested before thymectomy. Thus blood T cells in MG showed functional signs of preactivation (high sensitivity to rIL-2 alone) without detectable CD25 expression on fresh cells, raising the possibility of aberrant IL-2 receptor regulation and/or expression in MG T cells. Decreased sensitivity to rIL-2 after thymectomy, associated with general clinical improvement, suggests a role for activated cells originating from the thymus in the pathogenesis of MG, and is of clinical relevance in patient follow-up. Our findings also provide a new approach in the study of MG pathogenesis: the search for aberrant immunoregulation mechanisms linked to defects in lymphokine circuits.
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PMID:High recombinant interleukin-2 sensitivity of peripheral blood lymphocytes from patients with myasthenia gravis: correlations with clinical parameters. 278 27

Addition of recombinant interleukin-2 (rIL-2) to normal adult murine thymocytes in vitro as the only exogenous stimulus leads to a dose-dependent mitogenic response characterized by two distinct dosage kinetic components. The high-affinity IL-2 thymocyte response is mounted by in vivo-activated (IL-2 receptor light chain positive) thymocytes, while the low-affinity IL-2 response, of larger amplitude, is carried out by resting thymocytes. Addition of IL-2 to thymocytes also triggers intense IL-3 secretory responses with both high and low IL-2 affinity components. Addition of high IL-2 dosages to thymocyte bulk cultures results in a dramatic increase in IL-2 responsiveness for both proliferation and IL-3 secretion on a per viable cell basis and with tightly coupled temporal kinetics. The low-affinity component of IL-2-proliferative and IL-3-secreting responses is carried out by resting mature CD4+ thymocytes, as assessed by negative selection with monoclonal antibodies (mAb) plus complement. The mechanism of resting thymocyte activation by high doses of IL-2 is partially characterized. Depletion of endogenous thymus-adherent cells abolished both proliferation and IL-3 secretion, and addition of splenic accessory cells or peritoneal macrophages to depleted thymocytes restored IL-2 responsiveness. Mature CD4+ thymocytes spontaneously form rosettes with adherent accessory cells, while CD8+ thymocytes do so with much less efficiency. Rosette formation of CD4+, but not of CD8+ thymocytes, can be blocked by anti-CD4 mAb GK1.5. At the same dosage as it prevents rosette formation, mAb GK1.5 also blocks the low-affinity thymocyte response to IL-2. The high-affinity IL-2 response is completely resistant to the action of cyclosporin A (CsA), but the low-affinity IL-2 response, although of much larger amplitude, can be almost completely suppressed by CsA. Together, these results demonstrate that resting CD4+ thymocytes can be induced to proliferation and lymphokine secretion by IL-2 alone in a process that is dependent on interaction with accessory cells, involves CD4 adhesion molecules and triggers activation through a CsA-sensitive pathway. In addition, the results demonstrate that IL-2 alone is able to enhance thymocyte IL-2 responsiveness and IL-3 secretory responses in vitro. The ability of IL-2 to induce and maintain thymocyte function is discussed in the light of these results.
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PMID:Triggering of thymocyte function by IL-2 as the only exogenous stimulus; analysis of two distinct modes of IL-2-induced thymocyte proliferation and IL-3 secretion in vitro. 280 75

We evaluated the activation state of thymic lymphocytes in patients with myasthenia gravis (MG) by cytofluorographic analysis of CD25 expression and by testing their sensitivity to recombinant interleukin-2 (rIL-2) in the absence of any known previous stimulation. We detected no phenotypic signs of activation in fresh MG thymic lymphocyte suspensions, while functional signs of activation were reflected in a significantly higher sensitivity to rIL-2 in MG patients than in controls. The responses to rIL-2 were time- and dose-dependent, were inhibited by a blocking anti-IL-2 receptor antibody, and were associated with an increase in CD25+ T cells in both patients and controls. The T cells with functional signs of previous activation may represent autoreactive cells involved in the autoimmune process and confirm thymus gland hyperactivity in MG. These cells could result from primary autosensitization against the thymic acetylcholine receptor (AChR)-like molecule or from altered migration of peripheral activated cells into an abnormal thymic environment. Our results also provide a clue for understanding the effect of thymectomy in myasthenia gravis.
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PMID:Evidence of enhanced recombinant interleukin-2 sensitivity in thymic lymphocytes from patients with myasthenia gravis: possible role in autoimmune pathogenesis. 280 88

Considerable evidence now exists to support the notion that the 50-kDa sheep erythrocyte binding protein, T11, represents an essential cell surface component of a human T-cell-lineage activation pathway. Furthermore, it is known that the human T-cell antigen-major histocompatibility complex (MHC) receptor complex T3-Ti is capable of regulating cell growth mediated by the T11 structure. Here we show that, within the T3+ thymocyte compartment, T3-Ti crosslinking rapidly inhibits T11-initiated interleukin 2 (IL-2) gene transcription and translation. This inhibition is restricted to the IL-2 gene (IL2) as transcription of both the IL-2 receptor gene (IL2R) and the Ti beta-chain gene (TCRB) are not affected (human gene designations are in parentheses). Perhaps more importantly, T3-Ti-mediated IL-2 inhibition of this type is not operational in peripheral T lymphocytes. The results imply that the majority of T3+ thymocytes are functionally distinct from peripheral T lymphocytes despite their T3+ phenotype and may possess a unique endogenous regulatory component for suppressing IL-2 gene activity. Moreover, since IL-2 is likely rate-limiting for growth within the thymus, the findings provide one plausible mechanism for thymic selection--namely, T3-Ti crosslinking of thymocytes upon interaction with self-major histocompatibility complex inhibits clonal expansion of high-affinity autoreactive cells.
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PMID:Selective inhibition of interleukin 2 gene function following thymocyte antigen/major histocompatibility complex receptor crosslinking: possible thymic selection mechanism. 282 97

The growth of mature T lymphocytes is regulated by interaction between interleukin-2 (IL-2) and its receptor. Three distinct binding sites for IL-2, namely low- (Kd 10 nM), intermediate- (Kd 100 pM) and high- (Kd 10 pM) affinity sites, have been found on human and primate T lymphocytes. Chemical crosslinking of labelled IL-2 to human T cells shows that two polypeptide chains, p55 (L chain) and p75 (H chain), bind IL-2 with low and intermediate affinities respectively. The high-affinity binding was shown to arise from ternary complex formation of IL-2, L and H chains. Construction of mutants of the L-chain complementary DNA indicated that the L chain is not directly involved in growth signal transduction. Nevertheless, expression of the IL-2 receptor L chain is tightly regulated by antigen or mitogen stimulation. To investigate the L chain function, we have produced transgenic mice using human L-chain cDNA of the IL-2 receptor under the control of a constitutive promoter. Studies on the L-chain transgenic mice showed that functionally active IL-2 receptors with high affinity were expressed on unstimulated spleen and thymus cells. The results indicate that the H chain of the IL-2 receptor is constitutively expressed in T cells.
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PMID:Expression of functional interleukin-2 receptors in human light chain/Tac transgenic mice. 282 38

The surface of dendritic cells from mouse spleen, thymus, and epidermis has been compared with a panel of monoclonal antibodies and the FACS. A method was first developed to isolate populations of large, adherent, thymic dendritic cells that were greater than 90% pure. These were released by collagenase digestion and separated from adherent macrophages after overnight culture. Enrichment was based on the facts that most macrophages remained plastic adherent and rosetted strongly with antibody-coated erythrocytes. As in spleen, thymic dendritic cells were stellate in shape, had abundant class I and II MHC products, lacked many standard macrophage and lymphocyte markers, and actively stimulated the mixed leukocyte reaction. Most spleen and thymic dendritic cells could be lysed by the 7D4 mAb, to the low-affinity IL-2 receptor, and complement but the levels of 7D4 by FACS were low and sometimes not above background. Differences among dendritic cells from different tissues were noted with other mAb. Adherent dendritic cells from thymus all expressed the J11d "B cell" antigen and the NL145 interdigitating cell marker, but lacked the 33D1 spleen dendritic cell antigen. Eighty to ninety percent of spleen dendritic cells were J11d-, NL145-, 33D1+ but the remainder expressed the J11d+, NL145+, 33D1- thymic phenotype. The latter phenotype also was identical to that of epidermal Langerhans' cells. We postulate that the major 33D1+ cell in spleen represents a migratory stage in which dendritic cells are moving from tissues to lymphoid organs.
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PMID:The cell surface of mouse dendritic cells: FACS analyses of dendritic cells from different tissues including thymus. 291 Apr 99

Mature T cells arise from progenitor cells by a complex and poorly understood process of differentiation in the thymus. Thymocytes can be divided into four major compartments on the basis of surface expression of the murine equivalents of CD8 (Lyt-2) and CD4 (L3T4) (refs 1,2). Functionally mature thymocytes express only CD4 or CD8. The CD4-8- subset contains progenitor cells capable of giving rise to all the phenotypic and functional classes of T cells on adoptive transfer. The function of the major population, the CD4+8+ cells, which carry both the CD4 and CD8 antigens, in thymic differentiation is controversial. It has been variously proposed that they represent terminally differentiated cells which die in the thymus or that they represent an intermediate stage and can differentiate into functionally and phenotypically mature single positive T cells. The CD3-antigen receptor complex is probably important in thymic differentiation. The receptor has two functions: recognition and transmembrane signalling. To help clarify the function of CD4+8+ thymocytes in thymic differentiation, the expression and function of the antigen receptor complex on these cells should be determined. We show here that most CD4+8+ thymocytes express CD3 which functions in transmembrane signalling. The consequences of this signalling differ from those in mature T cells, however, in that the CD4+8+ cells do not secrete IL-2, express IL-2 receptor, or proliferate.
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PMID:Expression and function of the CD3-antigen receptor on murine CD4+8+ thymocytes. 295 67

There is no clear evidence that helper function is thymus dependent in the Common American newt, Notophthalmus viridescens. Here we test the capacity of concanavalin A, wheat germ agglutinin, human rIL-1 and rIL-2, reagents which stimulate T cell activities in other species, to substitute for carrier priming in the newt. Cytofluorimetric analyses have been used to demonstrate specific IL-2 receptor binding sites on newt splenocytes. Competitive pre-binding with rIL-2 tested whether anti-IL-2 receptor antibody binding sites would bind rIL-2. While Con A can substitute for carrier priming in the newt only when it is presented on Sepharose or agarose particles, wheat germ agglutinin cannot, even when it is injected in particulate form. Additionally, human rIL-1 can serve as an effective substitute for carrier priming, but rIL-2 cannot. The cytofluorimetric data are in agreement with the functional data in that they suggest that human rIL-2 may not bind newt splenocytes. Our data which show shared lectin specificities with T cell regulated helper function in another amphibian species are consistant with the possibility that T-like cells are responsible for helper function in this species.
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PMID:The substitution of carrier priming of helper function in the common American newt, Notophthalmus viridescens by lectins and human lymphokines. 296 62


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