Biomedical subjects

H Wang

Publications and source records attributed to H Wang.

At least 19 recordsLinked to original sources

PubMed1992

Effects of ecotropic murine retroviruses on the dual-function cell surface receptor/basic amino acid transporter.

The widely expressed Na(+)-independent transporter for basic amino acids (system y+) is the cell surface receptor (ecoR) for ecotropic host-range mouse retroviruses (murine leukemia viruses (MuLVs)), a class of retroviruses that naturally infects only mice or rats. Accordingly, expression of mouse ecoR cDNA in mink CCL64 fibroblasts yields cells (CEN cells) that have y+ transporter activity above the endogenous background and that bind and are infected by ecotropic MuLVs. The effect of ecotropic MuLV infection on expression of y+ transporter was analyzed in mouse and in mink CEN fibroblasts. Chronic infection with ecotropic MuLVs caused 50-70% loss (down-modulation) of mouse y+ transporter in plasma membranes, detected as a reduced Vmax for uptake and outflow of L-[3H]arginine with no effect on Km values. Down-modulation was specific for mouse y+ and did not affect other transporters or the endogenous mink y+, suggesting that it results from specific interaction between mouse y+ and the viral envelope glycoprotein gp70 in the infected cells. Because this partial loss of mouse y+ from cell surfaces is insufficient to explain the complete interference to superinfection that occurs in cells chronically infected with ecotropic MuLVs, alternative explanations for interference are proposed. In contrast to the y+ down-modulation caused by chronic infection, binding of extracellular envelope glycoprotein gp70 at 37 degrees C resulted in noncompetitive inhibition of amino acid import by mouse y+ but had no effect on export through this same transporter or on any transporter properties of mink y+. The effects of gp70 on transport kinetics suggest that it slows the rate-limiting step of the amino acid import cycle, a conformational transition of the empty transporter in which the binding site moves from the inside back to the outside of the cell, and that gp70 has no effect on the rate-limiting step of the amino acid export cycle. Infected cells retain substantial y+ activity. Moreover, the virus binding site on ecoR is in a mobile region that changes conformation during the amino acid transport cycle.

3T3 Cells↗

PubMed1992

Adoptive transfer of V beta 2-deleting activity with host cells from mice implanted with C4 preneoplastic hyperplastic alveolar nodules.

Selective deletion of mature peripheral V beta 2+ T-cells was observed in BALB/c mice implanted with the syngeneic C4 preneoplastic hyperplastic alveolar nodule (HAN) but not in mice with sham surgery (W. Z. Wei, R. Ficsor-Jacobs, S. J. Tsai, and R. Pauley, Cancer Res., 51:3331-3333, 1991). We now report the participation of host cells in that process. Peripheral V beta 2+ T-cells were reduced by 50% or more 4 weeks after an i.v. injection of 10 x 10(6) spleen cells from C4 HAN-bearing mice. Both T- and B-cell-enriched splenocytes mediated V beta 2 deletion. Secondary adoptive transfer of splenocytes from the recipients of the primary adoptive transfer also resulted in V beta 2+ T-cell deletion. The splenocytes lose V beta 2-deleting activity after 500 rad irradiation. V beta 2 deletion induced by either C4 HAN or splenocytes was more profound in CD4+ than in CD8+ T-cells. Loss of V beta 2+CD4+ T-cells was observed 5 days after the adoptive transfer of splenocytes, whereas V beta 2+ CD8+ cells were not reduced until day 9 or later. The differential rate of V beta 2+ CD4+ and CD8+ T-cell reduction continued for at least 7 weeks after the adoptive transfer. The pattern of V beta 2 deletion and the sequence of T-cell loss is similar in the recipients of C4 HAN or of adoptively transferred splenocytes. Southern blot analysis demonstrates non-germ line Mtv or MMTV proviral DNA in C4 HAN. Splenocytes of C4 HAN-bearing mice express a higher level of 1.7-kilobase long terminal repeat transcript than normal BALB/c splenocytes, suggesting a role for a unique Mtv/MMTV provirus in V beta 2 deletion.

Animals↗

PubMed1992

Interaction of immune sera with synthetic peptides corresponding to the structural protein region of hepatitis C virus.

Comparison of the deduced amino acid sequence from the structural region of the Hutchinson strain of hepatitis C virus (HCV-H) with four other HCV isolates clearly divides the five isolates into two groups based on sequence homology. The first group includes HCV-H, HCV-1, and HC-J1, while the second includes HCV-J1 and HC-J4. Among the five isolates the first 190 residues (putative nucleocapsid) are highly conserved whereas residues 196-513 exhibit significant diversity and include a hypervariable region encompassing residues 386-404. A series of overlapping decapeptides were synthesized by solid-phase pin technology according to sequence from HCV-H (amino acids 1-513), HC-J4 (amino acids 181-513), and regions from the three other isolates which exhibited sequence variation. A modified ELISA was used to measure immunoreactivity of sera from clinical posttransfusion cases and experimentally infected chimpanzees. Comparison of pre- and postinfection samples revealed 16 clusters of immunoreactive peptides within the structural region, none of which was found in the hypervariable region. Only one cluster (amino acids 73-89) was recognized by all human and chimpanzee sera. Clear variation in the immune response was observed between individuals, although no obvious difference in reactivity between acute and chronic cases was observed. Within individual profiles, the reactivity to each peptide cluster and the total number of reactive clusters increased over time.

Amino Acid Sequence↗

PubMed1992

Studies of CD4- CD8- alpha beta bone marrow T cells with suppressor activity.

The predominant T cell subset in the bone marrow of specific pathogen-free C57BL/Ka and BALB/c mice expressed the alpha beta+ TCR CD4- CD8- surface phenotype. Purified C57BL/Ka alpha beta+ TCR CD4- CD8- marrow cells obtained by cell sorting suppressed the MLR of C57BL/Ka responder and BALB/c stimulator spleen cells. Although the percentage of typical T cells in the spleen was markedly reduced in adult nude mice or normal neonatal mice as compared to the normal adult, the percentage of alpha beta+ TCR CD4- CD8- cells in the spleen and marrow was not. The percentage of "self-reactive" V beta 5+ T cells in the BALB/c spleen was markedly reduced as compared to that in the C57BL/Ka spleen. However, the percentages in the bone marrow were similar. The results indicate that the predominant subset of marrow T cells in these pathogen-free mice differ with regard to surface marker phenotype, function, dependence on the adult thymus, and deletion of certain self-reactive V beta receptors as compared to typical spleen T cells. The marrow T cells appear to develop directly from marrow precursors without rearranged beta chain genes during a 48 hour in vitro culture.

Animals↗

PubMed1992

Ibuprofen improves survival but does not ameliorate increased gut mucosal permeability in endotoxic pigs.

Intravenous lipopolysaccharide (LPS) decreases superior mesenteric arterial blood flow and increases ileal mucosal permeability in pigs. We tested the hypothesis that these phenomena can be ameliorated by pretreatment and posttreatment with ibuprofen. Pentobarbital-anesthetized immature swine were mechanically ventilated (fraction of inspired oxygen, 0.5) and infused with Ringer's lactate (RL) solution (0.8 mL/kg per minute). Animals in group RL (n = 10) received no other interventions. Animals in group RL + LPS (n = 15) were infused with LPS (50 micrograms/kg) from a time range equal to 0 through 60 minutes. Animals in group RL + LPS + ibuprofen (n = 10) were similarly infused with LPS, but in addition, they received ibuprofen (10 mg/kg at -30 minutes and 10 mg/kg per hour from -30 through 210 minutes). Intestinal permeability was assessed by measuring plasma-to-lumen clearances of two hydrophilic probes (chromium 51-labeled edetic acid monohydrate [EDTA] and urea) and by expressing the results as a clearance ratio (CEDTA/CUREA). Survival was 100%, 67%, and 100% in groups RL, RL + LPS, and RL + LPS + ibuprofen, respectively. Among survivors only, CEDTA/CUREA increased significantly over time in both endotoxic groups, but not in nonendotoxic controls. Treatment with ibuprofen transiently blocked LPS-induced mesenteric hypoperfusion. These data indicate that mediators other than cyclooxygenase-derived metabolites of arachidonic acid are responsible for the adverse effect of LPS on mesenteric permeability to hydrophilic solutes in this porcine model.

Animals↗

PubMed1992

Human monoclonal and polyclonal anti-human immunodeficiency virus-1 antibodies share a common clonotypic specificity.

Human monoclonal and purified polyclonal anti-human immunodeficiency virus (HIV)-1 antibodies were tested for binding to a murine monoclonal anti-idiotypic antibody (1F7, IgM, kappa). Four human monoclonal anti-p24 and three human monoclonal anti-gp120 antibodies express the 1F7 clonotype, while one human monoclonal anti-gp41 antibody does not bind to 1F7. Affinity-purified anti-p24 and anti-gp120 antibodies from HIV-1-infected individuals also react with 1F7. Western blot analysis and enzyme-linked immunosorbent assay confirmed that 1F7 reacts with human antibodies of different HIV-1 antigen specificities. A survey of sera from 329 HIV-1-infected individuals showed binding to 1F7 in 239 sera (72.6%) while 1F7 was not reacting with 109 HIV-1-negative sera. These results show that 1F7 idiotype is an HIV-1 infection-associated clonotypic marker shared by anti-HIV-1 antibodies with different epitope specificites.

Antibodies, Anti-Idiotypic↗

PubMed1992

cDNA sequence of three cysteine-rich clusters in the iron-sulfur subunit of complex II (succinate-ubiquinone oxidoreductase) from Caenorhabditis elegans determined by automated DNA sequencer.

Homology probing by using mixed primers for polymerase chain reaction (PCR) and a subsequent sequence analysis by automated DNA sequencer were applied to determine a partial cDNA sequence of the iron-sulfur subunit of complex II (succinate-ubiquinone oxidoreductase). Complex II is a membrane-bound flavoenzyme, which catalyzes the oxidation of succinate to fumarate in the tricarboxylic acid cycle, and it is a component of the mitochondrial and bacterial respiratory chains. In this study, the partial amino acid sequence of iron-sulfur subunits in Caenorhabditis elegans mitochondria was deduced from the DNA sequence obtained from cDNA-PCR. Mixed oligonucleotide primers corresponding to two conserved regions which appear to be the binding site for the prosthetic group were used. The product of PCR was cloned into plasmid vector pUC 119 and the sequence was determined from double strand plasmid DNA by the dideoxy method using of one-dye, four-lane type the automated DNA sequencer (DSQ-1, Shimadzu). The PCR product contained 483 nucleotides and its deduced amino acid sequence was highly homologous with that in human liver (68.9%) and that of Escherichia coli sdh B product (50.3%). As expected, striking sequence conservation was found around the three cysteine-rich clusters which have been thought to comprise the iron-sulfur centers of the enzyme.

Amino Acid Sequence↗

PubMed1992

Repression of SV40 T oncoprotein expression by DMSO.

SV40 large T oncoprotein-transformed murine mesenchymal 3T3 T stem cells (CSV3 cells) can be induced to growth arrest and then differentiate into adipocytes. When differentiation occurs, SV40 T oncoprotein expression is repressed (Estervig et al., J Virol 63:2718, 1989). To determine if repression of T oncoprotein expression can also be induced pharmacologically, the effect of a variety of agents that have been reported to effect differentiation in various cell types but not in 3T3 T or CSV3 cells was tested. This rationale suggests that if any of these agents repress T oncoprotein expression in CSV3 cells, then the results would establish that repression of T oncoprotein expression can be mediated by mechanisms independent of overt differentiation. The results show that dimethylsulfoxide (DMSO) is the only agent tested that represses T oncoprotein expression in CSV3 cells. Repression occurs in a dosage-dependent manner within 24-96 hours after exposure to DMSO. The effect of DMSO on T oncoprotein expression is mediated by posttranslational mechanisms that decrease the stability of the T oncoprotein. DMSO-induced repression of T oncoprotein expression is also associated with reversion of the transformed phenotype in CSV3 cells as demonstrated by the loss of responsiveness to a specific transformation-associated mitogen. These data support the conclusion that the pharmacological repression of T oncoprotein expression represents a form of cancer suppressor activity that can be mediated by a distinct molecular mechanism.

Acetamides↗

PubMed1992

An mRNA that specifically accumulates in maize roots delineates a novel subset of developing cortical cells.

A near full-length cDNA clone (pZRP3) corresponding to an mRNA that accumulates specifically in roots of maize was isolated. The ZRP3 mRNA is ca. 600 nucleotides in length. The amino acid sequence of the predicted polypeptide is rich in leucine (16%), proline (11%), and cysteine (8.5%). The zrp3 gene appears to be expressed exclusively in roots, whereas other ZRP3-related genes are expressed in additional organs of the maize plant. In situ hybridization shows that ZRP3 mRNA accumulation is largely confined to the cells of the cortical ground meristem. Furthermore, accumulation of this mRNA occurs within a distinct subset of cortical cells, the inner three to four cell layers.

Amino Acid Sequence↗

PubMed1992

Suppression of human nasopharyngeal carcinoma cell growth in nude mice by the wild-type p53 gene.

Wild-type and mutant human p53 genes were transfected into the nasopharyngeal carcinoma (NPC) cell line CNE-3. Tumorigenicity in nude mice showed that the tumor resulting from the cells transfected with the wild-type p53 gene grew more slowly and was smaller than that from the cells transfected with mutant p53 gene and that from control CNE-3 cells. In contrast, the tumor from the cells transfected with the mutant p53 gene grew faster than that produced by cells transfected with the wild-type p53 gene and that produced by control CNE-3 cells. The results demonstrate that the wild-type p53 gene could inhibit the NPC cell growth in nude mice and the mutant p53 gene could enhance the NPC cell growth in nude mice. The p53 gene may also play an important role in the pathogenesis of NPC.

Animals↗

PubMed1992

A colorimetric method for detection of specific ligand binding.

The binding of IL-2 and IL-3 to the factor-dependent cell lines CTB6 and 32D, respectively, was determined using biotinylated ligand detected by the addition of a streptavidin/alkaline phosphatase conjugate and amplified with a phosphatase amplification system. Binding of both ligands was detectable after incubation with as little as 20 fmol of ligand and could be inhibited with a 10-fold molar excess of nonbiotinylated ligand. No binding was observed when biotinylated ligand was incubated with a receptor negative cell line (PC-12) and IL-2 was unable to compete with biotinylated IL-3 binding to 32D cells, further demonstrating specificity. These studies indicate that biotinylated ligands can be used as a nonradioactive method to detect specific, high-affinity cell surface receptors.

Alkaline Phosphatase↗

PubMed1992

Induction of c-jun independent of PKC, pertussis toxin-sensitive G protein, and polyamines in quiescent SV40-transformed 3T3 T cells.

CSV3 clones of simian virus 40 large T antigen-transformed murine 3T3 T cells can be made quiescent as part of a differentiation process. In these quiescent cells, insulin- and vanadate-induced mitogenesis are both associated with the induction of the c-jun proto-oncogene (Wang and Scott 1991 J. Cell. Physiol. 147, 102-110; Wang et al. 1991 Cell Growth Differ. 2, 645-652). The current studies were therefore designed to compare the early signal transduction pathways employed by insulin and vanadate to regulate c-jun expression. In quiescent CSV3-1 cells, down-regulation of protein kinase C by prolonged exposure to 12-O-tetra-decanoylphorbol-13-acetate or inhibition of protein kinase C activity by treatment with the protein kinase C antagonist staurosporine is shown not to affect c-jun induction by insulin or vanadate. This suggests that both insulin and vanadate act in a protein kinase C-independent manner. Insulin's effect on c-jun induction does, however, involve a G protein because insulin's effect can be inhibited by pertussis toxin. In contrast, vanadate induction of c-jun is not affected by pertussis toxin. Genistein, a general tyrosine kinase inhibitor, can inhibit the ability of vanadate to induce c-jun but it does not inhibit insulin's effect. Finally, the depletion of polyamines, particularly spermidine, by DL-alpha-difluoromethylornithine treatment also prevents c-jun induction by insulin but DL-alpha-difluoromethylornithine treatment has no effect on c-jun induction by vanadate. These observations indicate that the c-jun induction by insulin and vanadate in CSV3-1 cells is mediated by different signal transduction mechanisms. Together with our previously published data, these results suggest that c-jun can be induced independent of protein kinase C activation, without involvement of pertussis toxin-sensitive G protein, independent of induction of c-fos, and without expression of high levels of intracellular polyamines.

3T3 Cells↗

PubMed1992

Water binding capacity of mixtures of lens crystallins.

The water binding capacity of mixtures of bovine lens crystallins were investigated by combined differential scanning calorimetry and thermogravimetric analysis techniques. Binary, ternary and quaternary mixtures of alpha, beta H, beta L, and lower molecular weight (LMW) crystallins were prepared in proportion of their natural abundance. The percentage of non-freezable water of the total water content was used as an index of the bound water in all these mixtures and it was obtained as a function of crystallin concentration. These experimental values were compared to theoretical values that were calculated from the water binding capacity of individual crystallins obtained previously [Bettelheim and Popdimitrova (1990) Exp. Eye Res. 50, 715-8]. The calculations were based on the assumption that the mixtures of crystallins have the same intermolecular interactions that exist in the individual crystallins. Thus, the difference between the experimental and theoretical curves is an indicator of the type of interactions that may exist among the different crystallins. In all mixtures the experimental bound water was higher than the theoretical, predicted value at physiological concentrations. The water binding capacity of the lyophilized thin lens sections, on the other hand, was lower than the theoretical, predicted value.

Animals↗

PubMed1992

The effects of rubidium, caesium and quinine on 5-HT-mediated behaviour in rat and mouse--1. Rubidium.

The administration of TCP (15 mg/kg, i.p.) to rats pretreated with either intraperitoneal RbCl (3 mmol/kg, twice daily for 5 days) or dietary RbCl (30 mmol/kg diet, for 14 days), resulted in the complete 5-HT behavioural syndrome. Pretreatment with p-chlorophenylalanine (i.p. 300 mg/kg x2) or (-)-propranolol (20 mg/kg, i.p.), pindolol (4 mg/kg, i.p.) and ritanserin (0.4 mg/kg, s.c.) prevented the occurrence of the 5-HT syndrome, produced by dietary RbCl plus TCP. Intraperitoneal administration of RbCl had no effect upon the 5-HT behavioural syndrome, produced by 8-OH-DPAT (0.5 mg/kg, s.c.) or 5-MeODMT (2 mg/kg, i.p.) but enhanced the 5-HT syndrome produced by quipazine (20 mg/kg, i.p.), DOI (8 mg/kg, s.c.), p-chloramphetamine (4 mg/kg, i.p.) or by TCP plus L-tryptophan (50 mg/kg, i.p.) in rats. Dietary administration of RbCl resulted in the enhancement of the 5-HT2-mediated head-twitches in the mouse and the attenuation of hypothermia in the mouse, induced by 8-OH-DPAT (0.5 mg/kg, s.c.). The accumulation of 5-HT (after inhibition of monoamine oxidase) and the rate of synthesis of 5-HT in the whole brain (minus cerebellum) were enhanced by dietary and intraperitoneal administration of RbCl, respectively. The effects of lithium and rubidium, respectively, on 5HT function in brain are compared.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1992

The effects of rubidium, caesium and quinine on 5-HT-mediated behaviour in rat and mouse--2. Caesium.

Rats and mice were given either CsCl (3 mmol/kg, s.c.) or saline (as control), twice daily for 3 days. The administration of tranylcypromine (TCP) (15 mg/kg, i.p.) to rats pretreated with CsCl produced the 5-HT behavioural syndrome. Pretreatment with CsCl also enhanced the syndrome induced by p-chloroamphetamine (3 mg/kg, i.p.) or by TCP (15 mg/kg, i.p.) plus L-tryptophan (50 mg/kg, i.p.). p-Chlorophenylalanine (300 mg/kg, i.p., daily on 2 consecutive days) or (-)-propranolol (20 mg/kg, i.p.), pindolol (4 mg/kg, i.p.) and ritanserin (0.4 mg/kg, s.c.), all prevented the behavioural syndrome induced by CsCl and TCP in rats. Pretreatment of rats with CsCl potentiated the 5-HT syndrome, elicited by the 5-HT agonists, 8-OH-DPAT (0.5 mg/kg, s.c.), 5-MeODMT (2 mg/kg, s.c.) and quipazine (25 mg/kg, i.p.). Pretreatment with CsCl potentiated the 5-HT2-mediated head-twitches in the mouse but had no effects on hypothermia in the mouse induced by 8-OH-DPAT (0.5 mg/kg, s.c.). The rate of synthesis of 5-HT in the whole brain (excluding cerebellum) was enhanced by pretreatment with CsCl. The enhancement of 5-HT neuronal function by caesium may be related to its ability to block K(+)-channels in neuronal membranes.

Animals↗

PubMed1992

The effects of rubidium, caesium and quinine on 5-HT-mediated behaviour in rat and mouse--3. Quinine.

It has been shown that caesium, which shares properties with quinine as a K(+)-channel blocker, enhanced 5-HT-mediated behaviour in both rats and mice. It was therefore of interest to investigate the effects of quinine on 5-HT-mediated behaviour in the rat and mouse. Quinine, dose-dependently (ED50 = 5 mg/kg), produced the 5-HT behavioural syndrome in rats pre-treated with tranylcypromine (TCP) (15 mg/kg, i.p.). p-Chlorophenylalanine (i.p., 300 mg/kg x2) or (-)-propranolol (20 mg/kg, i.p.), pindolol (4 mg/kg, i.p.) and ritanserin (0.4 mg/kg, s.c.), all prevented the behavioural syndrome induced by quinine (72 mg/kg, i.p.) plus TCP. The administration of quinine (72 mg/kg, i.p.) enhanced the 5-HT syndrome elicited by p-chloramphetamine (4 mg/kg, i.p.) and the 5-HT agonists, 8-OH-DPAT (0.5 mg/kg, s.c.), 5-MeODMT (2 mg/kg, i.p.), DOI (8 mg/kg, s.c.) and quipazine (25 mg/kg, i.p.) in rats. Pretreatment with quinine also potentiated the 5-HT2-mediated head-twitch in the mouse but had no effect on the hypothermia in the mouse, induced by 8-OH-DPAT (0.5 mg/kg, s.c.). Quinine also enhanced the rate of synthesis of 5-HT in the brain of the rat. On the basis of these findings, together with those in the preceding two papers, it is suggested that the effects of rubidium, caesium and quinine, to enhance differentially various aspects of 5-HT function are mediated by actions on 5-HT-modulated K(+)-channels. This conclusion is also discussed in relation to the actions of lithium and electroconvulsive shock on 5-HT function in brain and the treatment of manic-depressive disease.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1992

Fibroblastoid cells derived from rat bone marrow and lung differ in their pattern of production of hemopoietic stimulators and inhibitors.

Blood cells develop in the bone marrow, controlled by a complex network of regulatory factors, some of which originate in the non-hemopoietic stroma. Previously we found that the predominant fibroblastoid (FB) cell growing in primary cultures of rat marrow bears surface antigens different from similar cells derived from certain other tissues. As determined by two monoclonal antibodies, the 'marrow type' is ST3+/ST4-, and the 'peripheral type' is ST3-/ST4+. Here we describe some of the functional differences between these two cell types. After primary cultures were depleted of hemopoietic elements and 'other' type FB, colony-stimulating activity was detected in the conditioned media (CM) of cells derived from marrow (ST3+), but not from lung (ST4+). Conversely, lung FB produced a CM that inhibited the clonogenic growth of normal marrow precursors. This substance (or substances) was produced by lung cells in the absence of exogenous stimulation, but by marrow cells only after they had been cultured in the presence of macrophage-derived products. The inhibitory activity did not have any measurable effect on murine blood cell precursors. We conclude that these isolated antibody-defined fibroblast subpopulations from different organs differ in their capacity to stimulate or inhibit normal hemopoietic precursors.

Animals↗

PubMed1992

Evidence for the existence of IL-4 and IFN gamma secreting cells in the T cell repertoire of naive mice.

The kinetics with which IgE responses develop in vivo following immunization of experimental animals indirectly support the existence of IL-4-secreting T cells as a normal component of the T cell repertoire. At the same time, studies of IL-4-secreting cell frequencies directly ex vivo have argued that T cells with the potential to become IL-4 secretors exist in vivo, in the form of precursors requiring stimulation and 4-12 days of culture as well as restimulation with mitogen or Ag before they become detectable as lymphokine-secreting cells. We demonstrate here that intravenous administration of low doses of anti-CD3 mAb 145-2C11 results in IL-4 production within 60 min of stimulation as demonstrated by Northern analysis of mRNA and a sensitive, selective bioassay (CT.4S cell proliferation) of biologically active IL-4 protein. Production of IL-4 is paralleled by IFN gamma synthesis, displaying similar kinetics. These findings, consistent with the presence of mature cells capable of IL-4 and IFN gamma synthesis in the T cell repertoire of naive mice, are supported by the observation that stimulation of spleen cells from naive mice with anti-CD3 mAb in vitro for 12 h also results in strong IL-4 and IFN gamma mRNA and protein synthesis. The data support and extend those obtained through analysis of cytokine mRNA synthesis alone, thereby providing evidence that "fresh" T cells are indeed capable of producing IL-4 directly ex vivo and are consistent with the existence of IL-4-secreting cells as a normal component of the T cell repertoire of naive mice.

Animals↗