Biomedical subjects

N Vita

Publications and source records attributed to N Vita.

At least 19 recordsLinked to original sources

PubMed2001

Neurotensin induces mating in Saccharomyces cerevisiae cells that express human neurotensin receptor type 1 in place of the endogenous pheromone receptor.

Heterologous expression of the human neurotensin receptor type I (hNT1-R) has been achieved in the yeast Saccharomyces cerevisiae. Immunoanalysis of membranes prepared from cells expressing a c-myc-tagged version of hNT1-R revealed multiple c-myc cross-reacting polypeptides of high molecular mass, suggesting that hNT1-R was glycosylated in yeast. High-affinity binding sites for 125I-labeled-[monoiodo-Tyr3]neurotensin ([125I-Tyr3]NT) were detected on hNT1-R-expressing cells with Kd and Bmax values of 3.2 nM and of 500 receptors per cell, respectively. Competition binding studies of neurotensin with SR142948 and SR48692, two nonpeptidic antagonists of hNT1-R, indicated that the yeast-produced recombinant receptor displayed the same pharmacological properties as hNT1-R expressed in mammalian cells. Interestingly, neurotensin activated the pheromone pathway in hNT1-R-expressing cells in a dose-dependent fashion, as revealed by a beta-galactosidase activity assay with a pheromone-responsive Fus1:lacZ construct. Mutational inactivation of the SST2 and STE2 genes increased the level of beta-galactosidase activity in response to neurotensin by twofold. Recombinant hNT1-R-producing cells, which lacked the endogenous G-protein-coupled receptor for the alpha pheromone, mated with wild-type MATalpha haploid cells in response to neurotensin, leading to bona fide diploid zygote formation. This is the first report of a mammalian receptor that can replace the endogenous pheromone receptor when produced in yeast, by signaling a fully effective, agonist-induced, mating process.

Binding, Competitive↗

PubMed2001

Functional characterization of neurotensin receptors in human cutaneous T cell lymphoma malignant lymphocytes.

Cutaneous T cell lymphomas are a clonal proliferation of CD4+ T lymphocytes primarily involving the skin. Mycosis fungoides is an epidermotropic CD4+ cutaneous T cell lymphoma, and a more aggressive form, Sezary syndrome, occurs when the malignant cells become nonepidermotropic. The role of neuropeptides in the growth and chemotaxis capacity of cutaneous T cell lymphoma cells remains unknown. In this report, we found that cutaneous T cell lymphoma cells, similarly to normal resting or activated peripheral lymphocytes, were able to bind neurotensin. We used an interleukin-2-dependent cutaneous T cell lymphoma malignant T cell line derived from cutaneous T cell lymphoma lesions in order to study the role of neurotensin in the proliferation and migration of these malignant cells. First, we determined that the malignant cells expressed neurotensin receptors on their cell membrane. Functional results indicated that neurotensin did not stimulate the growth of the cell line. In contrast, this neuropeptide inhibited the proliferation of the tumor cells in response to exogenous interleukin-2. Furthermore, we found that neurotensin enhanced both spontaneous and chemoattractant-induced migration of the malignant cells. This suggests that neurotensin in skin can play a role in the disease by locally limiting the growth of the cutaneous T cell lymphoma tumor cells in response to cytokines and by enhancing their chemotaxis capacity.

CD4-Positive T-Lymphocytes↗

PubMed2000

Anti-inflammatory effects of peripheral benzodiazepine receptor ligands in two mouse models of inflammation.

In vivo treatment of mice with peripheral benzodiazepine receptor ligands exerts an inhibitory effect on the inflammatory response in two models of acute inflammation. In the first model, pretreatment of the animals (24 h) with 1-(2-chlorophenyl)-N-methyl-N(1-methylpropyl)-3-isoquinoline carboxamide (PK11195) and 7-chloro-5-(4-Chlorophenyl)-1, 3-dihydro-1-methyl-2-H-1,4-benzodiazepin-2 (Ro5-4864), at different doses (0.00001-10 mg/kg, i.p.) dose dependently inhibited the formation of mouse paw oedema induced by carrageenan with mean ID(50s) of 0.009 (95% confidence limits=0.0076-0.013) and 0.04 (95% confidence limits=0.025-0.0086) mg/kg, respectively. Both ligands (0. 1 mg/kg, i.p.) inhibited in the same way the mouse paw oedema induced by carrageenan in animals with and without adrenal glands. PK11195 and Ro5-4864 (0.1 mg/kg, i.p.) inhibited the mouse paw oedema induced by several inflammatory mediators. In the second model, the pretreatment (24 h) with peripheral benzodiazepine receptor ligands (0.1 mg/kg, i.p.) exerted an inhibitory effect on neutrophil influx and produce a marked inhibition of carrageenan-produced interleukin-13 and interleukin-6 in pleural exudation. Our results extend previous findings that peripheral benzodiazepine receptor is involved in the inflammatory response, and suggest that this action may be linked to the action of different inflammatory mediators, probably mainly by the inhibition of the release of pro-inflammatory cytokines.

Animals↗

PubMed2000

Innate recognition of bacteria in human milk is mediated by a milk-derived highly expressed pattern recognition receptor, soluble CD14.

Little is known about innate immunity to bacteria after birth in the hitherto sterile fetal intestine. Breast-feeding has long been associated with a lower incidence of gastrointestinal infections and inflammatory and allergic diseases. We found in human breast milk a 48-kD polypeptide, which we confirmed by mass spectrometry and sequencing to be a soluble form of the bacterial pattern recognition receptor CD14 (sCD14). Milk sCD14 (m-sCD14) concentrations were up to 20-fold higher than serum sCD14 from nonpregnant, pregnant, or lactating women. In contrast, lipopolysaccharide (LPS)-binding protein was at very low levels. Mammary epithelial cells produced 48-kD sCD14. m-sCD14 mediated activation by LPS and whole bacteria of CD14 negative cells, including intestinal epithelial cells, resulting in release of innate immune response molecules. m-sCD14 was undetectable in the infant formulas and commercial (cows') milk tested, although it was present in bovine colostrum. These findings indicate a sentinel role for sCD14 in human milk during bacterial colonization of the gut, and suggest that m-sCD14 may be involved in modulating local innate and adaptive immune responses, thus controlling homeostasis in the neonatal intestine.

Amino Acid Sequence↗

PubMed2000

Cutting edge: human B cell function is regulated by interaction with soluble CD14: opposite effects on IgG1 and IgE production.

The mechanism(s) controlling activation of naive B cells, their proliferation, Ag receptor affinity maturation, isotype switching, and their fate as memory or plasma cells is not fully elucidated. Here we show that between 24 and 60% of CD19+ cells in PBMC bind soluble CD14 (sCD14). Tonsillar B cells also bind sCD14, but preferentially the CD38-ve/low cells. Interaction of sCD14 with B cells resulted in higher levels of IgG1 and marked inhibition of IgE production by activated tonsillar B cells and Ag-stimulated PBMC. We found that sCD14 interfered with CD40 signaling in B cells, inhibited IL-6 production by activated B cells, and increased the kinetics and magnitude of CD40 ligand expression on T cells. Together with the previously reported effects on T cells, these findings define sCD14 as a novel soluble regulatory factor capable of modulating cellular and humoral immune responses by interacting directly with T and B cells.

B-Lymphocyte Subsets↗

PubMed1999

Soluble CD14 acts as a negative regulator of human T cell activation and function.

T cell activation is controlled by the coordination of stimulatory and negative regulatory signals which are not completely defined. In this study we tested for a possible direct effect of CD14 on the regulation of T cell activation and function. We show that soluble CD14 (sCD14) induces inhibition of antigen-mediated peripheral blood mononuclear cells (PBMC) proliferation and anti-CD3-mediated proliferation of CD4+CD8+, CD4+CD8+ and CD4+CD8+ Tcell clones. This effect is not due to cell death, but results from a marked inhibition of IL-2 production. Proliferation of T cell clones due to exogenous IL-2 is not affected by sCD14. We also found that sCD14 inhibits production of another Th1-like cytokine, IFN-gamma and a Th2-like cytokine, IL-4. Importantly, sCD14 induces a progressive accumulation of the inhibitory protein IkappaB-alpha. We show that sCD14 binds to activated T cells. Following cell activation, biotinylated sCD14 stains CD3+ PBMC, as well as human T cell clones with varying intensity. The binding is saturable, can be inhibited by excess of unlabeled sCD14 and, following binding, sCD14 is internalized. Collectively, these findings reveal a previously unrecognized function of sCD14, namely its capacity to negatively regulate T lymphocyte activation and function by interacting directly with activated T cells.

Biological Transport, Active↗

PubMed1999

In vitro functional evidence of different neurotensin-receptors modulating the motor response of human colonic muscle strips.

1. The newly developed non-peptide neurotensin (NT)-receptor antagonists SR 48692 and SR 142948 were used to challenge NT responses of human colonic circular smooth muscle strips in vitro. The presence of NT1 and NT2 receptor transcripts in this tissue was tested by reverse transcriptase polymerase chain reaction (RT - PCR) analysis. 2. NT potently and dose-dependently contracted muscle strips, with significant regional differences in potency and efficacy between the transverse and distal colon: EC50, 3.6 and 7.5 nM; the maximal effect was 70 and 55% of 0.1 mM carbachol. Colonic responses to NT in both segments were virtually the same in the presence of atropine (1 microm), levocabastine (10 microM) or tetrodotoxin (1 microM). 3. SR 142948 (10 nM - 1 microM) competitively antagonized NT responses in the transverse and distal colon with similar affinities: pA2 values 8.71 and 8.45, slopes 0.98 and 0.99. SR 48692 (10 nM - 10 microM) antagonized the NT response competitively in the distal colon (pA2 6.55, slope 0.79) and non-competitively in the transverse colon (pA2 8.0, slope 0.51). Neither compound had any agonist effect. 4. The fact that the specific antagonists prevented NT-evoked atropine- and tetrodotoxin-insensitive mechanical responses of colonic muscle strips is highly consistent with the presence in these tissues of non-neuronal NT receptors, whose heterogeneity in the transverse segment is supported by the non-competitive antagonism of SR 48692. The finding of NT1 receptor transcript in both transverse and distal colon suggests its identity with the lower affinity site disclosed functionally by SR 48692 in these segments.

Aged↗

PubMed1998

Neurotensin is an antagonist of the human neurotensin NT2 receptor expressed in Chinese hamster ovary cells.

The human levocabastine-sensitive neurotensin NT2 receptor was cloned from a cortex cDNA library and stably expressed in Chinese hamster ovary (CHO) cells in order to study its binding and signalling characteristics. The receptor binds neurotensin as well as several other ligands already described for neurotensin NT1 receptor. It also binds levocabastine, a histamine H1 receptor antagonist that is not recognised by neurotensin NT1 receptor. Neurotensin binding to recombinant neurotensin NT2 receptor expressed in CHO cells does not elicit a biological response as determined by second messenger measurements. Levocabastine, and the peptides neuromedin N and xenin were also ineffective on neurotensin NT2 receptor activation. Experiments with the neurotensin NT1 receptor antagonists SR48692 and SR142948A, resulted in the unanticipated discovery that both molecules are potent agonists on neurotensin NT2 receptor. Both compounds, following binding to neurotensin NT2 receptor, enhance inositol phosphates (IP) formation with a subsequent [Ca2+]i mobilisation; induce arachidonic acid release; and stimulate mitogen-activated protein kinase (MAPK) activity. Interestingly, these activities are antagonised by neurotensin and levocabastine in a concentration-dependent manner. These activities suggest that the human neurotensin NT2 receptor may be of physiological importance and that a natural agonist for the receptor may exist.

Amino Acid Sequence↗

PubMed1998

The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled receptor.

In this work, the 100-kDa neurotensin (NT) receptor previously purified from human brain by affinity chromatography (Zsürger, N., Mazella, J., and Vincent, J. P. (1994) Brain Res. 639, 245-252) was cloned from a human brain cDNA library. This cDNA encodes a 833-amino acid protein 100% identical to the recently cloned gp95/sortilin and was then designated NT3 receptor-gp95/sortilin. The N terminus of the purified protein is identical to the sequence of the purified gp95/sortilin located immediately after the furin cleavage site. The binding of iodinated NT to 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid-solubilized extracts of COS-7 cells transfected with the cloned cDNA was saturable and reversible with an affinity of 10-15 nM. The localization of the NT3 receptor-gp95/sortilin into intracellular vesicles was in agreement with previous results obtained with the purified receptor and with gp95/sortilin. Affinity labeling and binding experiments showed that the 110-kDa NT3 receptor can be partly transformed into a higher affinity (Kd = 0.3 nM) 100-kDa protein receptor by cotransfection with furin. This 100-kDa NT receptor corresponded to the mature form of the receptor. The NT3/gp95/sortilin protein is the first transmembrane neuropeptide receptor that does not belong to the superfamily of G-protein-coupled receptors.

Adaptor Proteins, Vesicular Transport↗

PubMed1998

Regulation of interleukin-13 receptor constituents on mature human B lymphocytes.

Human B cells stimulated through both their immunoglobulin and CD40 receptors up-regulate 745 +/- 51 interleukin (IL)-13 ligand binding sites with an affinity of 0.91 +/- 0.08 nM within 24 h. IL-13 binds primarily to the IL-13Ralpha1 with subsequent sequestration of the IL-4Ralpha into the complex. IL-13Ralpha1 may also be found in those receptors capable of binding IL-4. gamma chain (gammac) participates in receptors capable of binding IL-4 but is not found in association with bound IL-13. Dimeric receptors composed of the IL-4Ralpha complexed with either the IL-13Ralpha1 or gammac occur simultaneously within defined B cell populations. mRNAs for all receptor constituents are increased subsequent to immunoglobulin stimulation alone, while maximal expression of IL-13Ralpha1 is more dependent upon co-stimulation of immunoglobulin and CD40 receptors. mRNA levels for IL-13Ralpha1 vary over a wider range subsequent to surface stimulation than other receptor components. Although gammac is not bound to IL-13 in B cells under the conditions evaluated, it may influence IL-13 binding by competing with IL-13Ralpha1 for association/sequestration with the IL-4Ralpha chain. IL-13Ralpha2 does not participate in the IL-13 receptor that is up-regulated upon activation of quiescent tonsillar B lymphocytes, although mRNA for the protein may be found in the centroblastic fraction of tonsillar cells.

B-Lymphocytes↗

PubMed1998

Identification and location on syndecan-1 core protein of the epitopes of B-B2 and B-B4 monoclonal antibodies.

Using a phage display peptide library, we characterized the epitope of two monoclonal antibodies reacting with syndecan-1: B-B2 and B-B4. The identified epitopes QDIT, for B-B2, and LPEV, for B-B4, were found to align with residues 36-39 and 90-93 of the mature protein, respectively. In contrast to B-B4, the B-B2 epitope is close to a potential glycosaminoglycan attachment site. Since syndecan-1 is heavily glycosylated and post-translational modifications are cell type specific, these results might explain the differences observed in the reactivity pattern of B-B2 and B-B4 and suggest that these monoclonal antibodies are useful probes to study cell surface exposed syndecan-1.

Amino Acid Sequence↗

PubMed1998

High affinity RGD-binding sites at the plasma membrane of Arabidopsis thaliana links the cell wall.

The heptapeptide Tyr-Gly-Arg-Gly-Asp-Ser-Pro containing the sequence Arg-Gly-Asp (RGD--the essential structure recognised by animal cells in substrate adhesion molecules) was tested on epidermal cells of onion and cultured cells of Arabidopsis upon plasmolysis. Dramatic changes were observed on both types of cells following treatment: on onion cells, Hechtian strands linking the cell wall to the membrane were lost, while Arabidopsis cells changed from concave to convex plasmolysis. A control heptapeptide Tyr-Gly-Asp-Gly-Arg-Ser-Pro had no effect on the shape of plasmolysed cells. Protoplasts isolated from Arabidopsis cells agglutinate in the presence of ProNectinF, a genetically engineered protein of 72 kDa containing 13 RGD sequences: several protoplasts may adhere to a single molecule of ProNectinF. The addition of the RGD-heptapeptide disrupted the adhesion between the protoplasts. Purified plasma membrane from Arabidopsis cells exhibits specific binding sites for the iodinated RGD-heptapeptide. The binding is saturable, reversible, and two types of high affinity sites (Kd1 approximately 1 nM, and Kd2 approximately 40 nM) can be discerned. Competitive inhibition by several structurally related peptides and proteins noted the specific requirement for the RGD sequence. Thus, the RGD-binding activity of Arabidopsis fulfils the adhesion features of integrins, i.e. peptide specificity, subcellular location, and involvement in plasma membrane-cell wall attachments.

Arabidopsis↗

PubMed1997

Accurate topological comparison of two recombinant human growth hormones by optical surface plasmon resonance.

A strategy for the comparison of two recombinant derived human growth hormones (r-hGH) has been developed using surface plasmon resonance (SPR). Statistical analysis was systematically used on the results obtained with several batches derived from two different Escherichia coli strains. Monoclonal antibodies (MAb) directed against four different domains in the tertiary structure of natural human growth hormone were used to compare the epitopic maps of the three (two recombinant and one natural) hGH by SPR analysis. Topological studies show the homogeneity of the epitopic maps of the three hGH. The kinetic parameters, association rate, and dissociation rate constants were also analyzed for the binding of each hGH batch to all MAbs. They were found to be homogeneous between the three hormones. Furthermore, the two r-hGH were compared by more classical approaches examining recognition of lactogenic or somatogenic receptors using, respectively, a bioassay of Nb2 cell proliferation and binding to rat liver microsomes. Specific bioactivities and IC50 values calculated in radioreceptor assays did not significantly differ between different r-hGH. The method was sensitive enough to show slight differences on koff value for one MAb (3C11) between (natural) hormone and two r-hGH. These differences are discussed in relation to previous observation made in the literature and the presence of isoforms in the natural product. The strategy developed here was very useful as a new tool to establish the equivalence of the two r-hGH.

Analysis of Variance↗

PubMed1997

Detection and biochemical characteristics of the receptor for complexes of soluble CD14 and bacterial lipopolysaccharide.

Soluble CD14 (sCD14) has been found to bind LPS and mediate LPS activation of several cell types. It has been postulated that sCD14-LPS complexes induce cell responses by interacting with a cell surface structure, which, in turn, triggers cell activation. There has been no biochemical evidence, however, for a direct interaction of sCD14 with a cell surface structure, and the putative receptor has not been identified. To rigorously test this hypothesis, we studied the interaction of human rsCD14 with cells in the absence of serum and in the presence and the absence of LPS. We found 1) there was specific and saturable binding of 125I-sCD14, indicative of a typical receptor-ligand interaction, to several cell types, including endothelial cells, epithelial cells, astrocytes, and human monocytes; 2) specific binding to all the cell types and IL-6 induction in membrane-bound CD14 (mCD14)-negative cells occurred only when both sCD14 and LPS were present; 3) competitive displacement experiments of 125I-sCD14 binding to astrocytes and Scatchard plots revealed a binding of high affinity (Kd = 3.3 +/- 0.4 nM) and approximately 25,000 single class binding sites/cell; 4) the steady state for the association of 125I-sCD14 was obtained after 180-200 min; 5) chemical cross-linking experiments revealed the association of sCD14 with a binding structure of approximately 216 kDa; 6) binding of 125I-sCD14 to CD14-expressing cell transfectants was about 50% lower than that to nontransfected cells. Maximal binding, however, was recovered after removing mCD14, suggesting that the sCD14-LPS receptor may also interact with mCD14. These results provide direct biochemical evidence for the existence of a cell surface signal-mediating binding structure for LPS-bearing sCD14 and suggest that this structure may represent the signaling unit of the postulated multimeric LPS receptor in mCD14-bearing cells.

Animals↗

PubMed1997

Cloning of the human IL-13R alpha1 chain and reconstitution with the IL4R alpha of a functional IL-4/IL-13 receptor complex.

The human homologue of the recently cloned murine IL-13 binding protein (IL-13R alpha1) was cloned from a cDNA library derived from the carcinoma cell line CAKI-1. The cloned cDNA encodes a 427 amino acid protein with two consensus patterns characteristic of the hematopoietic cytokine receptor family and a short cytoplasmic tail. The human protein is 74% identical to the murine IL-13R alpha1, and 27% identical to the human IL-13R alpha2. CHO cells expressing recombinant hIL-13R alpha1 specifically bind IL-13 (Kd approximately 4 nM) but not IL-4. Co-expression of the cloned cDNA with that of IL-4R alpha resulted in a receptor complex that displayed high affinity for IL-13 (Kd approximately 30 pM), and that allowed cross-competition of IL-13 and IL-4. Electrophoretic mobility shift assay showed that IL-13 and IL-4 were able to activate Stat6 in cells expressing both IL-4R alpha and IL-13R alpha1, while no activation was observed in cells expressing either one or the other alone.

Amino Acid Sequence↗

PubMed1997

Biochemical and pharmacological activities of SR 142948A, a new potent neurotensin receptor antagonist.

SR 142948A, 2-[[5-(2,6-dimethoxyphenyl)-1-(4-(N-(3-dimethylaminopropyl)-N-methylc arbamoyl)-2-isopropylphenyl)-1H-pyrazole3-carbonyl]amino] adamantane-2-carboxylic acid, hydrochloride, a new and extremely potent neurotensin (NT) receptor antagonist, has been characterized in comparison with SR 48692. This selective compound possesses nanomolar affinities for NT receptors, recognizes the two binding sites described for the NT receptor and fully displaces [3H]SR 48692 specific binding. SR 142948A antagonizes the classical in vitro NT effects, i.e., inositol monophosphate formation in HT 29 cells (IC50 = 3.9 nM) or intracellular calcium mobilization in Chinese hamster ovary cells transfected with the human receptor. It dose-dependently (0.04-640 x 10(-3) mg/kg p.o.) inhibits the turning behavior induced by unilateral intrastriatal injection of NT in mice, with the biphasic profile previously seen for SR 48692. At 0.1 mg/kg (i.p.), it completely antagonizes NT-evoked acetylcholine release in the rat striatum. In contrast to SR 48692, SR 142948A (p.o.) blocks both hypothermia and analgesia induced by i.c.v. injection of NT (mice and/or rats) but is unable to modify the dopamine release evoked by NT injection into the ventral tegmental area. In summary, SR 142948A retains the properties of the lead compound SR 48692 (no intrinsic agonist activity, oral bioavailability, long duration of action and good brain access), reveals a wider spectrum of activity than SR 48692 (probably due to the inhibition of NT receptor subtypes) and represents an additional tool for further exploration of the therapeutic potential of this class of compounds.

Adamantane↗

PubMed1997

Interleukin-13 responsiveness and interleukin-13 receptor expression in non-Hodgkin's lymphoma and reactive lymph node B cells. Modulation by CD40 activation.

Interleukin-13 (IL-13) responsiveness was examined in lymph node B cells from patients with non-Hodgkin's lymphoma (NHL) and patients with benign reactive immune disorders. Proliferation assays showed that NHL B cells from 8 of 21 patients responded to IL-13 in the absence of a co-activation signal. IL-13-unresponsive NHL B cells from 9 of the 13 remaining patients were induced to respond to IL-13 upon antibody-triggered CD40 activation, as did reactive B cells. Binding experiments with radiolabeled IL-13 revealed that the constitutive expression of IL-13 receptors (IL-13R) was associated with IL-13 responsiveness in the absence of CD40 activation. In IL-13-unresponsive cells, IL-13R expression was induced after CD40 activation. This effect was enhanced by IL-10, which was able to potentiate the IL-13 response of CD40-activated cells. Furthermore, IL-13 was found to increase the viability of cultured NHL cells, but not that of non-malignant cells. These results suggest that IL-13, which behaves as a potent co-factor for normal lymph node B cell activation, might provide growth and/or survival advantages to NHL B cells.

B-Lymphocytes↗

PubMed1997

The related cytokines interleukin-13 and interleukin-4 are distinguished by differential production and differential effects on T lymphocytes.

We have compared the production of the related cytokines IL-13 and IL-4 by T lymphocytes, and the effects of the two cytokines on these cells. IL-13 and IL-4 production differ in a number of respects. IL-13 is produced at higher levels than IL-4 by activated T lymphocytes, and its accumulation in the culture medium can be more prolonged, corresponding partly to differential mRNA accumulation and partly to a preferential depletion of IL-4 from the culture medium. Certain inducing combinations such as PMA and anti-CD28, stimulate high levels of IL-13 and IL-13 mRNA, but little or no IL-4 or IL-4 mRNA. The ratio of IL-13 to IL-4, both at protein and mRNA levels, is higher in CD8+ lymphocyte than in CD4+ lymphocyte populations. Although after in vitro polarization of peripheral blood lymphocytes leading to type 1 and type 2 populations, IL-13 is made principally by cells of a type 2 phenotype, as is IL-4; it can also be produced by type 1 CD4+ and CD8+ T lymphocyte clones making large amounts of IFN-gamma and very little IL-4. IL-13 and IL-4 exert different effects on T lymphocyte functions. IL-13 does not significantly inhibit the IL-2-induced T lymphocyte production of IFN-gamma, RANTES, MIP-1 alpha or MIP-1 beta, nor that of perforin mRNA, as does IL-4. We have also been unable to demonstrate STAT6 activation by IL-13 on T lymphocytes purified in a number of ways, despite strong activation of STAT6 by IL-4 in these cells. This is contrary to some previous reports, but is consistent with the notion that the majority of T lymphocytes lack functional IL-13 receptors. A higher and more prolonged T lymphocyte production of IL-13 than that of IL-4 may thus be permissible because IL-13 does not inhibit T-cell functions. Conversely, sustained IL-13 production may be partly due to the absence of receptor-mediated depletion of this cytokine.

Base Sequence↗