IL-2 Receptor Alpha Expression Research Articles

Cord Blood CD8+ T Cells Have a Natural Propensity to Express IL-4 in a Fatty Acid Metabolism and Caspase Activation-Dependent Manner.

How T cells differentiate in the neonate may critically determine the ability of the infant to cope with infections, respond to vaccines and avert allergies. Previously, we found that naïve cord blood CD4+ T cells differentiated toward an IL-4-expressing phenotype when activated in the presence of TGF-β and monocyte-derived inflammatory cytokines, the latter are more highly secreted by infants who developed food allergy. Here, we show that in the absence of IL-2 or IL-12, naïve cord blood CD8+ T cells have a natural propensity to differentiate into IL-4-producing non-classic TC2 cells when they are activated alone, or in the presence of TGF-β and/or inflammatory cytokines. Mechanistically, non-classic TC2 development is associated with decreased expression of IL-2 receptor alpha (CD25) and glycolysis, and increased fatty acid metabolism and caspase-dependent cell death. Consequently, the short chain fatty acid, sodium propionate (NaPo), enhanced IL-4 expression, but exogenous IL-2 or pan-caspase inhibition prevented IL-4 expression. In children with endoscopically and histologically confirmed non-inflammatory bowel disease and non-infectious pediatric idiopathic colitis, the presence of TGF-β, NaPo, and IL-1β or TNF-α promoted TC2 differentiation in vitro. In vivo, colonic mucosa of children with colitis had significantly increased expression of IL-4 in CD8+ T cells compared with controls. In addition, activated caspase-3 and IL-4 were co-expressed in CD8+ T cells in the colonic mucosa of children with colitis. Thus, in the context of colonic inflammation and limited IL-2 signaling, CD8+ T cells differentiate into non-classic TC2 that may contribute to the pathology of inflammatory/allergic diseases in children.

HIV Infection Deregulates the Balance Between Regulatory T Cells and IL-2–Producing CD4 T Cells by Decreasing the Expression of the IL-2 Receptor in Treg

Indexation of regulatory T cells (Treg) to the number of activated T cells constitutes a homeostatic mechanism ensuring that T-cell expansion remains under control. However, immune hyperactivation observed in HIV-infected patients suggests a possible dysfunction of this mechanism. Here we show that the Treg/IL-2-producing cells' balance is deeply disturbed in viremic HIV-infected patients. We found a lower expression of IL-2 receptor alpha on Treg from viremic patients. We confirmed in vitro that HIV infection of Treg downregulates IL-2 receptor alpha and phosphorylated STAT5. Our results argue for an impaired capacity of Treg to sense the expansion of activated T cells in HIV-infected patients that could contribute to the immune deregulation.

The Ikaros Transcription Factor Regulates Responsiveness to IL-12 and Expression of IL-2 Receptor Alpha in Mature, Activated CD8 T Cells

The Ikaros family of transcription factors is critical for normal T cell development while limiting malignant transformation. Mature CD8 T cells express multiple Ikaros family members, yet little is known about their function in this context. To test the functions of this gene family, we used retroviral transduction to express a naturally occurring, dominant negative (DN) isoform of Ikaros in activated CD8 T cells. Notably, expression of DN Ikaros profoundly enhanced the competitive advantage of activated CD8 T cells cultured in IL-12, such that by 6 days of culture, DN Ikaros-transduced cells were 100-fold more abundant than control cells. Expression of a DN isoform of Helios, a related Ikaros-family transcription factor, conferred a similar advantage to transduced cells in IL-12. While DN Ikaros-transduced cells had higher expression of the IL-2 receptor alpha chain, DN Ikaros-transduced cells achieved their competitive advantage through an IL-2 independent mechanism. Finally, the competitive advantage of DN Ikaros-transduced cells was manifested in vivo, following adoptive transfer of transduced cells. These data identify the Ikaros family of transcription factors as regulators of cytokine responsiveness in activated CD8 T cells, and suggest a role for this family in influencing effector and memory CD8 T cell differentiation.

Tec Kinase Inhibits the Expression of IL-2 Receptor Alpha (CD25) in Human T-Lymphocyte.

Activation and development of lymphocytes is regulated by the engagement of cell surface immune cell antigen receptors. Following receptor engagement, these receptors transmit signals by the activation of cytoplasmic protein tyrosine kinases (PTKs). The Tec PTK belongs to a group of structurally related nonreceptor PTKs that also includes Btk, Itk (Emt), Rlk (Txk), and Bmx (Etk). We have found the contribution of Tec in the antigen receptor signaling in B-lymphoid cells in the previous studies. Despite the presence of evidences suggesting the involvement of Tec in T-lymphocyte activation pathway via T-cell receptor (TCR) and CD28, the role of Tec in T-lymphocyte still remains unclear because of the lack of apparent defects in T-lymphocyte function in Tec-deficient mice. In this study, we investigated the role of Tec in T-lymphocyte using Jurkat human T-lymphoid cell line stably transfected with a cDNA encoding Tec. We found that the expression of wild type Tec but not kinase-deleted Tec inhibited the expression of IL-2 receptor alpha (CD25) induced by TCR cross-linking. The percentage of CD25 expressing cells after TCR cross-linking was 41.7% in mock-transfected cells, 18.3% in the wild type Tec expressing cells and 41.3% in the kinase-deleted Tec expressing cells. Second, the selective inhibitor of Tec family PTK, LFM-A13, rescued the suppression of TCR-induced CD25 expression observed in the wild type Tec-expressing Jurkat cells. We conclude that Tec PTK mediates signals that negatively regulate CD25 expression induced by TCR cross-linking, implying that this PTK plays a role in the attenuation of the IL-2 activity in human T-lymphocytes.

RELATIONSHIP BETWEEN HIGH-MOBILITY GROUP BOX 1 PROTEIN RELEASE AND T-CELL SUPPRESSION IN RATS AFTER THERMAL INJURY

To study whether high-mobility group box 1 protein (HMGB1) has an effect on T-cell-mediated immunity secondary to burn injury, 96 male Wistar rats weighing 250 to 300 g were randomly divided into three groups as follows:sham burn group, burn group, and burn with ethyl pyruvate treatment group, and they were killed on postburn days (PBDs)1, 3, 5, and 7, respectively, with 8 animals at each time point. Columns of nylon wool were used to isolate splenic T cells. T-Cell proliferation was analyzed with thiazolyl blue and expression of IL-2 receptor alpha (IL-2Ralpha) on the surface of T cell with flow cytometry. Levels of HMGB1 were determined using Western blot analysis. IL-2, soluble IL-2R, IL-4, and interferon-gamma were determined with enzyme-linked immunosorbent assay kits. Gene expressions of HMGB1, IL-2, and IL-2R were assessed using reverse-transcription polymerase chain reaction, and activation of nuclear factor of activated T cell was determined with gel mobility shift assay. The levels of HMGB1 in plasma were significantly elevated on PBDs 1 to 5. Significant proliferation of splenic T cells and IL-2, as well as IL-2Ralpha expression on T cells, were simultaneously suppressed to a certain extent on PBDs 1 to 7. Nuclear factor of activated T-cell activity of splenic T cells was markedly down-regulated on PBDs 1 to 3. Administration of ethyl pyruvate to inhibit HMGB1 can significantly restore proliferative activity, nuclear factor of activated T-cell activity, and expression levels of IL-2 and IL-2Ralpha on T cells. High-mobility group box 1 protein released after major burns might be associated with the pathogenesis of immunosuppression in splenic T lymphocytes in rats.

In vitro Immunomodulatory activities of a newly concocted traditional Chinese medicine formula: VI‐28

Previous studies have suggested that Vigconic VI-28, an anti-aging traditional Chinese medicine (TCM) formula containing Radix Ginseng and Cornu Cervi Pantotrichum, possesses immunological efficacy. This in vitro study further investigated the immunomodulatory effects of the hot water extracts of VI-28. The study included (1) colorimetric 5-bromo-2'-deoxy-uridine proliferation ELISA for estimating mitogenicity in human peripheral blood mononuclear cells (PBMC), (2) immunofluorescence staining for measuring the expression of IL-2 receptor alpha (CD25) on lymphocytes, (3) cytometric bead array (CBA) for quantifying cytokine liberation from PBMC, and (4) intracellular immunophenotyping for macrophage phagocytosis and hydrogen peroxide (H(2)O(2)) production from monocytes. The results demonstrated that VI-28 (1) could dose-dependently inhibited the proliferation of unstimulated and lipopolysaccharide-activated PBMC but enhanced the proliferation of phytohemagglutinin-activated PBMC at concentrations of <1 mg/mL, (2) significantly augmented the expression of CD25 on lymphocytes at concentrations of 0.4 mg/mL or above (p < 0.05), (3) dose dependently (0.1-1.0 mg/mL) activated macrophage phagocytosis and monocyte synthesis of H(2)O(2) and (4) significantly increased the production of cytokines IL-8, IL-10, IL-12 and IL-1beta at various concentrations of VI-28 (p < 0.05). The results suggest that VI-28 is a potential immunomodulator which probably acts through the activation of lymphocytes and monocytes.

Synergistic inhibitory activities of interleukin-10 and dexamethasone on human CD4+ T cells.

We have previously demonstrated that interleukin (IL)-10 synergizes with dexamethasone (Dex) in inhibiting proliferation of human T cells, stimulated in an antigen-presenting cell (APC)-dependent manner. Because IL-10 effectively inhibits APC accessory functions, the synergism could have been a result of its effect on APC. We then investigated the effects of Dex and IL-10 on T-cell subpopulations, stimulated in an APC-independent manner. CD4 and CD8 T cells were stimulated with anti-CD3, with or without Dex and IL-10, alone or in combination. Proliferation, glucocorticoid (GC) receptor binding, anti-CD3-induced tyrosine phosphorylation, IL-2 production, and expression of IL-2 receptor alpha, beta, and gamma chains were evaluated. The pharmacologic interactions were analyzed using the isobole method. IL-10 synergized with Dex in inhibiting CD4 but not CD8 T-cell proliferation. The synergism was not associated with modifications of GC receptor number or affinity, nor with modifications of anti-CD3-induced tyrosine phosphorylation. IL-10 synergized with Dex in inhibiting IL-2 production and increased Dex inhibitory effect on the expression of the IL-2 receptor alpha chain, which is up-regulated by CD3 stimulation and IL-2. Only Dex inhibited the beta and gamma chain expression, which, interestingly, is not up-regulated by IL-2. IL-2, as well as IL-7 and IL-15, reversed the effects of IL-10 but not those of Dex. IL-10 synergizes with Dex in inhibiting CD4 T-cell proliferation. Its synergizing effect is mediated by the inhibition of IL-2 production. Dex exerts additional activities, such as the inhibition of beta and gamma chain expression. Therefore, IL-10 could be useful for the enhancement of GC-based immunosuppressive therapies.

Binding of the hepatitis C virus envelope protein E2 to CD81 provides a co-stimulatory signal for human T cells.

Chronic hepatitis C virus (HCV) infection frequently develops into liver disease and is accompanied by extra-hepatic autoimmune manifestations. The tetraspanin CD81 is a putative HCV receptor as it binds the E2 envelope glycoprotein of HCV and bona fide HCV particles. Here we show that HCV E2 binding to CD81 on human cells in vitro lowers the threshold for IL-2 receptor alpha expression and IL-2 production, resulting in strongly increased T cell proliferation. HCV E2-induced co-stimulation also enhances the production of IFN-gamma and IL-4 and causes increased TCR down-regulation. This suggests that binding of HCV particles to CD81 on T cells in vivo may lead to activation by otherwise suboptimal stimuli. Therefore, co-stimulation of autoreactive T cells by HCV may contribute to liver damage and autoimmune phenomena observed in HCV infection.

Dual-color flow cytometric analysis of phenotype, activation marker expression, and proliferation of mitogen-stimulated bovine lymphocyte subsets

Bovine peripheral blood mononuclear cells were cultured in vitro for 3 days with the mitogens concanavalin A (Con A), pokeweed mitogen (PWM), phytohemagglutinin (PHA), and anti-CD3 monoclonal antibody. Activation of T-lymphocyte subsets (CD4 +, CD8 +, and γδ T-cell receptor +) and of B-cells was measured by two-color flow cytometric analysis of subset expression of IL-2 receptor alpha (CD25) and MHC class II. Proliferation of lymphocyte subsets was directly measured by two-color flow cytometric analysis of fluorescence intensity of PKH2, a fluorescent dye that stably incorporates into cell membranes. CD4 + and CD8 + T-cell subsets were stimulated by all the mitogens to increase expression of IL2r and MHC II and to proliferate. δγ + T-cells responded to all four mitogens with increased IL2r and MHC II expression. Con A and PHA caused measurable proliferation of γδ + T-cells, but PWM and anti-CD3 did not. B-cells generally responded to the mitogens with increased IL2r and MHC II expression. B-cells proliferated when incubated with Con A, but did not measurably proliferate in response to PWM, PHA, or anti-CD3.

Regulation of transcription factor NF kappa B in immune senescence.

The Rel/NF kappa B family of eukaryotic transcription factors are critical in immune and inflammatory processes regulating the expression of a wide variety of cytokines including IL-1, IL-2, IL-6, TNF-alpha and GM-CSF. Its ubiquitous distribution, rapid induction and regulation, the complexity of its subunits and its apparent involvement in several diseases has made this transcription factor a subject of intense study in normal cellular growth and cancer. Emerging studies have implicated a role for this transcription factor in the normal processes of aging. As significant declines in immune function is a natural concomitant to advancing age, the regulation of transcription factor NF kappa B appears to play a pivotal role in immune dysregulation during senescence, contributing to down regulation of both IL-2 and IL-2 receptor-alpha expression. Our studies have contributed to understanding the regulation of lowered NF kappa B induction in T cells during aging in humans and mice. Since we have shown that the lowered induction of NF kappa B in activated T cells from the elderly can be attributed to impaired degradation of the inhibitor I kappa B-alpha due to lowered proteasomal activity, we suspect that a similar alteration in proteasomal activity may be operative in age-dependent failure of immune function including the inability to initiate DNA synthesis following activation, skewing of T cell repertoire, lowered cytolytic activity and accumulation of aberrant proteins. Understanding the regulation of the proteasome pathway during immune senescence may provide new avenues for therapeutic intervention for immune based geriatric diseases.

A selective impairment of the IL-2 system in lymphocytes of patients with glioblastomas: increased level of soluble IL-2R and reduced protein tyrosine phosphorylation.

The occurrence of brain tumors is associated with broad suppression of the immune system function; however, the mechanisms involved in this impairment are not fully characterized. In this study, we have examined mechanisms involved in diminished T lymphocyte reactivity in patients with glioblastomas as compared to patients with other types of brain tumors. We found that the proliferative response of T lymphocytes stimulated with phytohemagglutinin or anti-CD3 was significantly reduced in these patients as compared to patients with meningiomas, oligodendrogliomas and healthy individuals. Stimulated T cells appear to express lower levels of the alpha-subunit (p55) of the IL-2 receptor (IL-2R), and increased levels of soluble IL-2R in cell supernatants, whereas no significant differences were observed in the level of the beta (p75)- or gamma-subunits. In addition, we found that competent T cells of glioblastoma patients exhibit lower levels of tyrosine phosphorylation in response to IL-2 as compared with cells of healthy donors. The decrease in the levels of IL-2 and its receptor was selective since no significant changes were observed in the secretion of other Th1- and Th2-derived cytokines (IFN-gamma and IL-4) and the expression of their respective receptors. These results indicate that the diminished response of T cells obtained from patients with glioblastomas may be due to a selective defect in the production of IL-2 and in the expression of functional IL-2R due to a decreased expression of the membranal IL-2R alpha and to lower levels of tyrosine phosphorylation in response to IL-2.

Ligand-induced autoregulation of IL-2 receptor alpha chain expression in murine T cell lines.

The IL-2 receptor (IL-2R) is composed of three chains alpha, beta and gamma. In mice, contrary to the human system, we have previously demonstrated that the IL-2R beta gamma complex does not bind IL-2. Therefore, mouse IL-2 response is completely dependent on the expression of the IL-2R alpha gene product. T cell clones expressing mouse IL-2R beta gamma and the human IL-2R alpha transgene have been studied. When cells are grown in IL-4, mouse IL-2R alpha is not expressed. However, exposure to IL-2 leads to the expression of the endogenous murine IL-2R alpha subunit. The T cell line expressing mouse IL-2R gamma and human IL-2R beta can grow in IL-2 but does not express endogenous murine IL-2R alpha. Transfection of these cells with the human IL-2R alpha gene restores the capacity to induce murine IL-2R alpha. This result demonstrates that IL-2-IL-2R alpha interactions are required for induction of IL-2R alpha. The kinetics of induction and deinduction of murine IL-2R alpha have been studied using clone 18.III. From negative cells, expression of murine IL-2R alpha is a very slow phenomenon. From cells fully expressing IL-2R alpha, deinduction is a two-step process: after a rapid decrease of IL-2R alpha the cells continue to express, for a long period of time, basal levels of murine IL-2R alpha. When cells expressing basal levels of IL-2R alpha are exposed to IL-2, induction of IL-2R alpha is a very rapid phenomenon. The autoregulatory loop formed by IL-2-IL-2R alpha therefore displays different levels of functioning.

Immunosuppreession induced bySalmonellainfection is correlated with augmentation of interleukin-2 receptor α chain expression in murine splenic lymphocytes

In a previous study, we observed that the suppression of T-cell proliferation induced by Salmonella cell-free extract was associated with augmentation of IL-2 receptor (IL-2R) alpha chain expression. In this study, we also observed this kind of augmentation of IL-2R alpha in Salmonella-infected mice. Phytohaemagglutinin (PHA)-stimulated proliferation of murine spleen cells was significantly suppressed when the mice were infected with Salmonella typhimurium. However, expression of the alpha chain but not the beta chain of IL-2R in lymphocytes was augmented by the infection. Analysis of the IL-2R-positive cell-population showed that the augmentation of IL-2R alpha was not specific to certain cell subpopulations. Furthermore, the inhibition of PHA-stimulated murine spleen cell proliferation and the augmentation of IL-2R alpha expression induced by the infection in lymphocytes was completely reversed by treatment with anti-interferon-gamma monoclonal antibody (anti-IFN-gamma Ab). These results suggest that the suppression of T-cell proliferation induced by Salmonella infection was associated with augmentation of IL-2R alpha expression in an IFN-gamma production-dependent manner in the same way as the suppression of T-cell proliferation induced by Salmonella cell-free extract.

Maturation of acute T-lymphoblastic leukemia cells after CD2 ligation and subsequent treatment with interleukin-2

In this study, we have investigated the ability of various cytokines to induce the maturation of acute lymphoblastic leukemia (T-ALL) cells with early T-cell phenotype. Leukemic blasts from 17 untreated T-ALL patients were assayed for their ability to acquire mature T-cell markers, CD3/T-cell receptor (TCR) in particular, after incubation with one or a combination of recombinant human interleukin-1 (IL-1), IL-2, IL-4, IL-7, and CD2-specific monoclonal antibody (MoAb). IL-7 or IL-2 induced the proliferation of some leukemic cells, whereas sequential cell treatment with CD2-MoAb and then IL-2 promoted CD3/TCR expression on nearly all CD2+ cells (15 of 16), except for 1 T-ALL that developed into CD3-CD16+CD56+ cells. Differentiation of T-ALL cells was also evidenced through the downregulation of CD34 precursor cell antigen, the generation of CD4+ and CD8+ cells from CD4+ CD8+ precursors, and the acquisition of mature T-cell functions. CD2 ligation induced a progressive increase of surface expression of IL-2 receptor alpha (IL- 2R alpha) and IL-2R beta and an accelerated in vitro death of leukemic cells. The ligation of IL-2R by IL-2 rescued T-ALL cells from death and promoted their progression toward more mature cells expressing extracellular CD3/TCR alpha beta complexes. Intracellular analysis indicates that TCR alpha transcription and membrane translocation of both TCR alpha and TCR beta were promoted in these conditions. Analysis of intracellular signals transduced during T-ALL differentiation indicated that CD2-ligation induced Ca2+ influx and that the ligation of CD2 and IL-2R induced distinct tyrosine phosphorylation patterns. The addition of inhibitors of tyrosine phosphorylation abolished T-ALL cell differentiation, which suggests the involvement of tyrosine kinases in this phenomenon. Together, we showed the constant maturation of leukemic early T cells after stimulation of surface CD2 and the high- affinity IL-2R.

Maturation of Acute T-Lymphoblastic Leukemia Cells After CD2 Ligation and Subsequent Treatment With Interleukin-2

In this study, we have investigated the ability of various cytokines to induce the maturation of acute lymphoblastic leukemia (T-ALL) cells with early T-cell phenotype. Leukemic blasts from 17 untreated T-ALL patients were assayed for their ability to acquire mature T-cell markers, CD3/T-cell receptor (TCR) in particular, after incubation with one or a combination of recombinant human interleukin-1 (IL-1), IL-2, IL-4, IL-7, and CD2-specific monoclonal antibody (MoAb). IL-7 or IL-2 induced the proliferation of some leukemic cells, whereas sequential cell treatment with CD2-MoAb and then IL-2 promoted CD3/TCR expression on nearly all CD2+ cells (15 of 16), except for 1 T-ALL that developed into CD3-CD16+CD56+ cells. Differentiation of T-ALL cells was also evidenced through the downregulation of CD34 precursor cell antigen, the generation of CD4+ and CD8+ cells from CD4+ CD8+ precursors, and the acquisition of mature T-cell functions. CD2 ligation induced a progressive increase of surface expression of IL-2 receptor alpha (IL-2R alpha) and IL-2R beta and an accelerated in vitro death of leukemic cells. The ligation of IL-2R by IL-2 rescued T-ALL cells from death and promoted their progression toward more mature cells expressing extracellular CD3/TCR alpha beta complexes. Intracellular analysis indicates that TCR alpha transcription and membrane translocation of both TCR alpha and TCR beta were promoted in these conditions. Analysis of intracellular signals transduced during T-ALL differentiation indicated that CD2-ligation induced Ca2+ influx and that the ligation of CD2 and IL-2R induced distinct tyrosine phosphorylation patterns. The addition of inhibitors of tyrosine phosphorylation abolished T-ALL cell differentiation, which suggests the involvement of tyrosine kinases in this phenomenon. Together, we showed the constant maturation of leukemic early T cells after stimulation of surface CD2 and the high-affinity IL-2R.

Immunosuppressive Effects of Azelastine Hydrochloride on Contact Hypersensitivity and T-Cell Proliferative Response: A Comparative Study with FK-506

Azelastine hydrochloride (AZE) is an anti-allergic drug that inhibits the release of various chemical mediators from mast cells. We compared the immunosuppressive effects of AZE and FK-506 in vivo and in vitro. Topical application of AZE strongly inhibited the efferent phase of contact hypersensitivity, as did application of FK-506. In in vitro experiments, we found that 1) the suppression by AZE on interleukin (IL)-2 production from splenic T cells was partial and considerably large amounts of IL-2 were still produced, even in the presence of 10(-5) M of AZE, which was in sharp contrast to the observed marked inhibition of [3H]-TdR incorporation; 2) AZE significantly inhibited the phorbol myristate acetate-induced IL-2 responsiveness; 3) AZE did not inhibit the IL-2 receptor alpha expression of activated T cells; and 4) the significant inhibitory action was still observed even when AZE was added at 48 h after the initiation of culture. In regard to FK-506, we found that 1) FK-506 completely blocked the production of IL-2; 2) exogeneous IL-2 consistently restored the FK-506-induced inhibition; 3) FK-506 affected the phorbol myristate acetate-induced IL-2 responsiveness very little, if any; and 4) the significant suppression was observed only when FK-506 was added within 24 h after the initiation of culture. Thus, AZE exerts its in vitro immunosuppressive activity preferentially by interfering with the IL-2 responsiveness, with partial inhibition of IL-2 production. Conversely, FK-506 acts as a strong inhibitor of IL-2 production without a prominent effect on IL-2 responsiveness. The immunosuppressive activity of AZE shown in vitro may also be operative in vivo and may be applicable for topical use.

Control of IL-2 receptor-alpha expression by IL-1, tumor necrosis factor, and IL-2. Complex regulation via elements in the 5' flanking region.

We have analyzed the mechanisms by which IL-1, IL-2, and TNF regulate expression of IL-2R alpha chain in a rodent T cell line. All three cytokines induce detectable IL-2R alpha mRNA by themselves, but there is strong synergy between IL-1 or TNF, on the one hand, and IL-2, on the other. The earliest phase of induction by IL-1 is independent of protein synthesis. IL-1, but not TNF, also stimulates transient secretion of IL-2. This leads to an autocrine stimulation of a further increase in IL-2R alpha mRNA levels. When IL-2 secretion has dropped off, continued IL-2R alpha expression requires both IL-2 and IL-1. Most or all of this regulation is due to changes in the rate of transcription of the IL-2R alpha gene. The response to IL-1 and IL-2 depends on a segment in the IL-2R alpha 5' flanking region, upstream of all cis-acting regulatory elements previously identified in the human gene.