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)

Natural killer cell stimulatory factor (NKSF) is a 70-kD heterodimeric cytokine that was initially isolated from conditioned medium of human B lymphoblastoid cell lines. The effects of recombinant NKSF on the function of human peripheral blood NK cells were examined. NKSF directly augmented the cytolytic activity of freshly isolated NK cells. Both CD56dim and CD56bright NK cells demonstrated enhanced cytotoxicity after brief exposure to NKSF. In contrast, highly purified T lymphocytes did not exhibit major histocompatibility complex-unrestricted cytotoxicity after short-term culture with NKSF. Like interleukin 2 (IL-2), NKSF augmented the lysis of NK-sensitive, NK-resistant, and antibody-coated targets. Both NKSF and IL-2 induced marked upregulation of several NK cell adhesion molecules known to participate in cytolysis, including CD2, CD11a, and CD54. However, NKSF activates NK cells through a pathway distinct from that of IL-2, since the presence of anti-IL-2 receptor (anti-IL-2R) antibodies or IL-4 did not inhibit the effects of NKSF. NKSF by itself induced very little proliferation of resting NK cells. NK cells preactivated in vitro with IL-2 demonstrated enhanced proliferation to NKSF, but the degree of proliferation was always inferior to that induced by IL-2 alone. Moreover, NKSF strongly inhibited IL-2-induced proliferation of either resting or preactivated NK cells. This inhibition was not the result of decreased IL-2R expression, because NKSF-activated NK cells expressed higher levels of both IL-2Rs p75 and p55. Furthermore, NKSF did not inhibit the proliferation of mitogen-activated T cells, indicating a selective effect on NK cell proliferation. Human NK cells expanded in vivo by prolonged continuous infusions of IL-2 remained fully responsive to NKSF. Picomolar concentrations of NKSF were as effective as nanomolar concentrations of IL-2 in augmenting the cytolytic activity of NK cells expanded in vivo by IL-2. NKSF may play an important role in the regulation of human NK cell function, and its possible use as a therapeutic cytokine deserves further investigation.
 ...
PMID:Response of human natural killer (NK) cells to NK cell stimulatory factor (NKSF): cytolytic activity and proliferation of NK cells are differentially regulated by NKSF. 134 96

Substantial proportions of resting B cells constitutively express low levels of IL-2 receptor (IL-2R) alpha and/or beta chains. The expression of these chains is differentially regulated by anti-IgM and IL-2/IL-4. The anti-IgM induces IL-2R alpha chain expression, whereas each of the two cytokines induces IL-2R beta chain expression in a dose-dependent manner. Moreover, IL-2 induces the growth of B cells, when the cells were pretreated with IL-2 or IL-4 for 24 h. The magnitude of this IL-2-driven B-cell growth depends upon the level of IL-2R beta chain expression. Costimulation of the B cells with IL-2 and anti-IgM shifts the dose-response curve, and the cells proliferate at an IL-2 concentration as low as 40 pM. These results indicate that the levels of anti-IgM-induced IL-2R alpha chain and IL-2-induced IL-2R beta chain determine the sensitivity of the cells to IL-2.
 ...
PMID:Role and regulation of interleukin (IL)-2 receptor alpha and beta chains in IL-2-driven B-cell growth. 137 2

Abnormalities in immune response play a major role in the increased susceptibility to infection after hemorrhage and trauma. Several studies have shown decreased release in vitro of interleukin-2 (IL-2) following blood loss. To better define in vivo the interactions between T and B cells, as well as the effects of treatment with the T cell-derived cytokines IL-2 and IL-4, mice were injected with concanavalin A at predetermined times posthemorrhage, and the percentages and numbers of splenic plasma cells producing antibody to the bacterial polysaccharide antigen levan (from Aerobacter levanicum) were determined. Decreased numbers and percentages of levan specific splenic plasma cells were found in animals treated with concanavalin A both immediately and 2 to 4 days after hemorrhage. Treatment in vivo with recombinant IL-2, but not IL-4 or anti-IL-2 receptor antibodies, following blood loss was able to increase the numbers of levan specific plasma cells to levels as high or higher than those found in normal, unhemorrhaged animals, but was unable to affect the decreased percentage of levan specific splenic plasma cells. These results suggest that the use in vivo of IL-2 may restore bacterial antigen specific antibody responses to normal levels after blood loss.
 ...
PMID:Modulation of the posthemorrhage bacterial polysaccharide antigen-specific antibody response by interleukins 2 and 4. 142 Jun 2

Lung involvement in patients affected by HIV-1 infection is characterized by an alveolitis sustained by the accumulation of CD8+ T lymphocytes. To investigate whether in situ T cell growth plays a relevant role in the pooling of CD8+ lymphocytes, we have analyzed the activity of two lymphokines involved in the mechanisms of T cell proliferation, i.e., interleukin-2 (IL-2) and interleukin-4. To this aim, following appropriate triggering and blocking, the expression and the functional role of IL-2 receptors (IL-2R) (both p55 and p75 chains) and IL-4 receptors have been analyzed on T lymphocytes obtained from the bronchoalveolar lavage (BAL) of 16 HIV-1+ patients. Molecular and phenotypic studies we performed demonstrated that CD8+ lymphocytes from the BAL of HIV-1 + patients strongly expressed the p75 chain of IL-2 receptor, while neither p55 mRNA nor its surface membrane product (Tac antigen) was detectable; in addition, there was no expression of IL-4 receptors. IL-2 stimulation was able to induce T cell growth in a dose-dependent manner, whereas IL-4 did not. Finally, using mAbs which specifically block the p55 or p75 IL-2R, we showed that both subunits of IL-2R were involved in the proliferative activity of lung lymphocytes. The results obtained in the present study directly demonstrate that BAL T lymphocytes of HIV-1 + patients express a fully functional IL-2 receptor apparatus, pointing to the role for this lymphokine in maintaining the alveolitis taking place in the lungs of AIDS patients.
 ...
PMID:Expression of a functional p75 interleukin-2 receptor on lung lymphocytes from patients with human immunodeficiency virus type 1 (HIV-1) infection. 143 Jan 8

The aim of this study was to examine the cytokine production and cytokine responsiveness of the first T-cell receptor (TcR) positive cells that appear in the murine fetal thymus, namely TcR V gamma 3 cells. It is shown that IL-2-cultured fetal TcR V gamma 3 thymocytes were capable of producing IL-3, GM-CSF, TNF-alpha and IFN-gamma upon TcR triggering. IL-2, IL-4, IL-5 and IL-6 could not be detected. With regard to cytokine responsiveness, TcR V gamma 3 cells proliferated to a high extent when high concentrations of rIL-2 were added. rIL-4 or rIL-7 alone, but not rIL-1 alone, were capable of inducing a modest proliferation of TcR V gamma 3 thymocytes. When combined with low concentrations of IL-2, a synergistic effect could be observed with IL-1, IL-4 or IL-7. It is shown that the synergistic effect of IL-2 with IL-4 was mainly due to induction of IL-2 receptor expression. The synergistic effect of IL-2 and IL-7 on the proliferation of TcR V gamma 3 cells could only be partially inhibited by anti-IL-2 receptor MoAb, and this antibody had no effect on the IL-2 + IL-1 cultures. These observations can explain the extensive proliferation of TcR V gamma 3 thymocytes during fetal life and they indicate that TcR V gamma 3 thymocytes have the potential to play a functional role during fetal thymus development.
 ...
PMID:Cytokine production and responsiveness of fetal T-cell receptor V gamma 3 thymocytes. 146 22

The calcium ionophore, A23187, when used alone was found to induce proliferation of murine T cells, at concentrations of 0.5-1 mM. This response required the presence of syngeneic splenic adherant cells (SAC) as a source of accessory cells. Interestingly, only CD4+ T cells but not CD8+ T cells or B cells responded to the calcium ionophore by proliferation. The inability of CD8+ T cells or B cells to respond was not related to decreased elevation in the intracellular ionized calcium [Ca2+]i concentration induced by the ionophore, because activated CD4+ T, CD8+ T and B cells all exhibited similar elevation in [Ca2+]i. The inability of CD8+ T cells to respond to calcium ionophore was probably due to insufficient production of autocrine growth factors, such as IL-2, inasmuch as the addition of exogenous IL-2 could completely restore the CD8+ T cell responsiveness. Also, exogenous rIL-1 could partially restore purified T cell response to calcium ionophore, whereas, rIL-6 failed to do so. IL-2, but not IL-4, acted as an autocrine growth factor for T cells responding to the calcium ionophore in the presence of SAC, since, antibodies against IL-2 or IL-2 receptor (IL-2R) but not against IL-4, could inhibit the T cell proliferation. Furthermore, exogenous rIL-2 but not rIL-4 supported the proliferation of T cells to calcium ionophore in the absence of accessory cells. Our results suggest that murine lymphocytes exhibit heterogeneity in their proliferative responsiveness to calcium ionophore and that this may not depend on the early activation signal such as the elevation in [Ca2+]i) induced by the ionophore but may depend on subsequent signals which regulate endogenous growth factor production.
 ...
PMID:Murine lymphocytes exhibit heterogeneity in their proliferative responsiveness to calcium ionophore. 148 6

The mechanism of peripheral immunological tolerance has not been fully established. While anergic T cells have been noted in tolerant hosts, the mechanism by which they contribute to the induction and maintenance of tolerance has not been defined. As we previously reported, an accelerated form of diabetogenic autoimmunity in nonobese diabetic mice can be blocked by passive transfer of a CD3+, CD8+, beta-chain variable region 11-positive islet-infiltrating T-cell clone (IS-2.15). In this report we examine the properties of this T-cell clone. We have established that this clone is unresponsive to mitogenic concentrations of anti-T-cell receptor or anti-CD3 monoclonal antibodies and is only weakly responsive to syngeneic islet and spleen cells. Moreover, these T cells secrete an inhibitory factor(s) that irreversibly inhibits interleukin (IL) 2/IL-4-driven proliferation of IL-2/IL-4 indicator T-cell lines. This noncytotoxic factor, which possesses an apparent size of 10-30 kDa, does not interfere with low-affinity IL-2 receptor expression. These data indicate that at least some anergic T cells can play an active role in peripheral tolerance by secreting suppressor factor(s) that regulate IL-2/IL-4-dependent proliferation.
 ...
PMID:An anergic, islet-infiltrating T-cell clone that suppresses murine diabetes secretes a factor that blocks interleukin 2/interleukin 4-dependent proliferation. 152 76

Granulomas around Schistosoma mansoni eggs are a principal cause of morbidity in mice infected with this helminth. In vivo treatment of infected mice with anti-IL-2 antibodies, with or without anti-IL-2 receptor antibodies, significantly diminished the size of circumoval granulomas in the liver and decreased hepatic fibrosis to half that in untreated mice. Antibody-treated animals also displayed a marked reduction in both peripheral blood and tissue eosinophilia while IgE levels were unchanged or increased. Spleen cell cytokine production in response to Ag or mitogen stimulation was selectively altered by in vivo anti-IL-2 administration. IL-5 responses were dramatically reduced, whereas IL-4, IL-2, and IFN-gamma responses were not consistently changed. These findings confirm previous observations, suggesting a role for IL-2 in egg-induced pathology but indicate that the primary function of this cytokine in schistosome-infected mice may be in the generation of Th2- rather than Th1-associated responses.
 ...
PMID:Treatment with anti-IL-2 antibodies reduces hepatic pathology and eosinophilia in Schistosoma mansoni-infected mice while selectively inhibiting T cell IL-5 production. 153 55

In adoptive immunotherapy, the number of effector cells is one of the major factors relating to the therapeutic efficacy. We demonstrated that tumor-infiltrating lymphocytes (TILs) were stimulated to proliferate by incubation with interleukin 2 (IL-2) plus interleukin 4 (IL-4). TILs cultured with IL-2 plus IL-4 increased 3.1-fold more than TILs cultured with IL-2 alone. However, IL-4 did not alter the cytotoxic activity of TILs against autologous tumor cells and established tumor cell lines. It is suggested that IL-2 receptor is related to the mechanism of the proliferation of activated TILs cultured by combination with IL-2 and IL-4. Thus, the combination of IL-2 and IL-4 may increase the efficacy of adoptive immunotherapy using activated TILs.
 ...
PMID:The promotive effect of interleukin 4 with interleukin 2 in the proliferation of tumor-infiltrating lymphocytes from patients with malignant tumor. 154 54

The capacity of staphylococcal enterotoxins to stimulate all T cells bearing certain TCR variable region alleles has generated a great deal of interest. This stimulation appears to involve specific binding of the toxin to class II molecules and subsequent stimulation of the T cell via the TCR V beta elements. Recent studies from our laboratory have focused on the ability of staphylococcal enterotoxins to directly activate purified lymph node T cells and a panel of T cell clones and hybridomas. A T cell costimulation assay was performed to assess cellular activation requirements and cytokine receptor expression. Activation of highly purified lymph node T cells by staphylococcal enterotoxin B (SEB) required costimulatory signals which could be provided by IL-1, IL-2, IL-4, or IL-6, whereas SEB alone demonstrated no significant proliferative response. Using a panel of TH1 and TH2 cell clones and T cell hybridomas possessing various responsive and nonresponsive V beta alleles, it was possible to demonstrate that SEA and SEB costimulate T cells via the TCR complex. Additionally, enterotoxin-pretreated T cells demonstrated a significant proliferative response upon exposure to class II-bearing accessory cells, suggesting that these toxins bind directly to T cells. Highly purified T cells cultured with both SEB and IL-1 exhibit significantly increased levels of IL-2 receptor, whereas cells cultured with SEB or IL-1 alone demonstrated low levels of this receptor. These results do not exclude an association of the staphylococcal enterotoxins with class II molecules in a manner which results in a high avidity binding to the TCR required for transduction of the appropriate activation signals. In the absence of class II molecules, however, these superantigens can still bind to T cells, and the activation signal is delivered in the presence of cytokines that trigger T cell growth and lymphokine production.
 ...
PMID:Direct activation of murine T cells by staphylococcal enterotoxins. 154 63


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