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PubMed1994

Developmental regulation of the orphan receptor COUP-TF II gene in spinal motor neurons.

Members of the steroid/thyroid hormone receptor superfamily are involved in the control of cell identity and of pattern formation during embryonic development. Chicken ovalbumin upstream promoter-transcription factors (COUP-TFs) can act as regulators of various steroid/thyroid hormone receptor pathways. To begin to study the role of COUP-TFs during embryogenesis, we cloned a chicken COUP-TF (cCOUP-TF II) which is highly homologous to human COUP-TF II. Northern analysis revealed high levels of cCOUP-TF II transcripts during organogenesis. Nuclear extracts from whole embryos and from embryonic spinal cords were used in electrophoretic mobility shift assays. These assays showed that COUP-TF protein is present in these tissues and is capable of binding to a COUP element (a direct repeat of AGGTCA with one base pair spacing). Analysis of cCOUP-TF expression by in situ hybridization revealed high levels of cCOUP-TF II mRNA in the developing spinal motor neurons. Since the ventral properties of the spinal cord, including the development of motor neurons, is in part established by inductive signals from the notochord, we transplanted an additional notochord next to the dorsal region of the neural tube in order to induce ectopic motor neurons. We observed that an ectopic notochord induced cCOUP-TF II gene expression in the dorsal spinal cord in a region coextensive with ectopic domains of SC1 and Islet-1, two previously identified motor neuron markers. Collectively, our studies raise the possibility that cCOUP-TF II is involved in motor neuron development.

Amino Acid Sequence↗
PubMed1986

[Antihypertensive action of dl-alpha-tocopherol 5-n-butyl-2-pyridinecarboxylate (TF-80)].

Antihypertensive action of TF-80, an alpha-tocopheryl ester of fusaric acid (FA), was studied in normotensive and hypertensive rats. Oral doses of TF-80 up to 100 mg/kg did not affect systolic blood pressure in Wistar rats, whereas 50 and 100 mg/kg doses produced a significant reduction in systolic blood pressure in both spontaneously hypertensive rats (SHR) and DOCA-salt hypertensive rats (DSR) without significant changes in heart rate. Although maximal reduction in systolic blood pressure at single oral dosing of TF-80 (50, 100 mg/kg) and FA (15, 30 mg/kg) was approximately the same extent, respectively, the antihypertensive action of TF-80 was longer-lasting than that of FA. TF-80 at a chronic administration of 1 to 100 mg/kg/day for 6-9 weeks was preventive to the generation of hypertension in young SHR and DSR, but FA did not prevent the generation of hypertension. Hypotensive doses of TF-80 did not interfere in the rise in blood pressure produced by vasoactive substances such as norepinephrine, prostaglandin F2 alpha and angiotensin II in SHR, and it also failed to inhibit plasma renin. TF-80 was also found not to have a diuretic effect. These results show that TF-80 has a mild and long-lasting antihypertensive action that is different from FA. However, the antihypertensive mechanism of TF-80 remains to be solved.

Animals↗
PubMed2004

Erythropoietin overcomes imatinib-induced apoptosis and induces erythroid differentiation in TF-1/bcr-abl cells.

Targeting BCR-ABL tyrosine kinase by treatment with the selective inhibitor imatinib (formerly STI571, Gleevec) has proved to be highly efficient for inhibiting leukemic growth in vitro. In addition, in clinical trials, imatinib has produced high response rates in patients with chronic myeloid leukemia (CML) in chronic phase and blastic crisis. However, episodes of severe cytopenia were also frequently observed, leading to discontinuation of therapy in some cases. Therefore, it is important to examine whether administration of cytokines overcomes the adverse effects of imatinib in in vitro systems. In this study, we examine the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO) on TF-1/bcr-abl (which was generated by transduction of a bcr-abl fusion gene into the TF-1 cell line) as a model system for CML with blastic crisis. Imatinib induced apoptosis in TF-1/bcr-abl cells but not in the parental TF-1 cells. However, GM-CSF, a survival factor of the parental TF-1 cells, protected TF-1/bcr-abl cells from imatinib-induced apoptosis in a dose-dependent manner. Concomitantly, constitutive phosphorylation of Stat5 and FKHRL1 was significantly inhibited by imatinib, and the inhibition was canceled by the addition of GM-CSF, accompanied by upregulation of Bcl-xL and downregulation of p27/Kip1. In addition, although untreated TF-1/bcr-abl cells had lost responsiveness to both GM-CSF and EPO and showed autonomous growth, GM-CSF enhanced phosphorylation of Stat5 and FKHRL1 in these cells. Importantly, imatinib-treated TF-1/bcr-abl cells differentiated into hemoglobin-positive cells in the presence of EPO, as in the case for the parental TF-1 cells. Taken together, imatinib-treated CML cells may differentiate into mature cells in the presence of differentiation-inducing cytokines such as EPO.

Apoptosis↗
PubMed2004

Inhibition of TF gene expression by antisense oligonucleotides in different cancer cell lines.

Human tissue factor (TF) is the initiator of blood coagulation. Beside this function it is involved in tumor angiogenesis and metastasis. In the study we have evaluated the efficiency of antisense oligonucleotides (AS-ODNs) against TF selected from computational prediction of TF mRNA structure. Fourteen different AS-ODNs were tested in three cell lines of different origin with a high TF content. In cell line MCF-7 expression of TF gene was inhibited up to 50% by the AS-ODN AS-7 in comparison to reference. To investigate the dependence of inhibition efficiency on the AS-ODN position inside a potential target motive we designed further AS-ODNs shifted 2-3 nt among AS-7. One AS-ODN was found as more effective than AS-7. In cell line T508 were obtained moderate effects in inhibition of TF gene expression of 30% by AS-4. In J82 cells TF protein was inhibited up to 68% by two AS-ODNs. In conclusion, we compared inhibition of TF gene expression in different cancer cell lines and found that all effective AS-ODNs were located in the translated region of TF mRNA. Suitability of a target region of an AS-ODN is relatively independent on cell line. In contrast, optimal transfection conditions are dependent on cell line.

Cell Line, Tumor↗
PubMed1988

Application of immobilized pH gradient isoelectric focusing to forensic hemogenetics: a survey on a three year experience with the transferrin (TF) and alpha 1-antitrypsin (PI) systems.

The subtypes of transferrin (TF) and alpha 1-antitrypsin (PI), first discovered using isoelectric focusing, are now mostly determined in immobilized pH gradient gels. We report on our experience in the parentage expertise with both polymorphisms over a period of three years. The complexity of the technology was compensated by the fact that most subtypes of TF and PI could be more reliably recognized. The PI alleles PI*M1, M2, M3, S, F, T, and Z and TF alleles TF*C1, C2 and C3, and in addition four further rare TF alleles were observed. The allele frequencies from non-related individuals did not deviate from the Hardy-Weinberg equilibria and corresponded well to known frequencies from West Germany and other Caucasoid populations. With the TF system 36 accused men, and with the PI system 54 were excluded from paternity from a total of 344 (TF) respectively 347 (PI) cases. From the data presented here isoelectric focusing in immobilized pH gradient gels appears to be a major improvement over carrier ampholyte generated pH gradients in the distinction of TF and PI phenotypes.

Alleles↗
PubMed1995

Isolation, characterization, and chromosomal localization of mouse and human COUP-TF I and II genes.

Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) are orphan members of the steroid/thyroid hormone receptor superfamily. COUP-TF homologues have been cloned in many species, from Drosophila to human. The protein sequences of COUP-TFs are highly homologous across species, suggesting functional conservation. Two COUP-TF genes have been cloned from human, and their genomic organizations have been characterized. To determine whether the genomic organization is conserved between human and mouse, we isolated two mouse COUP-TF genes (I and II) and characterized their genomic structures. Both genes have relatively simple structures that are similar to those of their human counterparts. In addition, we mapped mouse COUP-TF I to the distal region of chromosome 13 and COUP-TF II to the central region of chromosome 7. Furthermore, we mapped human COUP-TF I to 5q14 of chromosome 5 and COUP-TF II to 15q26 of chromosome 15. The results demonstrate that COUP-TF genes are located in chromosomal regions that are syntenic between mouse and human.

Animals↗
PubMed1993

Chicken ovalbumin upstream promoter transcription factor (COUP-TF): an orphan steroid receptor with a specific pattern of differential expression in human ovarian cancer cell lines.

The possible role of a novel steroid receptor in ovarian malignancy was investigated. The evolutionarily conserved orphan steroid receptor COUP-TF (chicken ovalbumin upstream promoter transcription factor) was originally identified as a protein interacting with an upstream promoter element of the chicken ovalbumin gene. The human receptor protein was purified from a cervical cancer cell line. An immunocytochemical technique for the visualization of COUP-TF was developed using a specific polyclonal rabbit antibody. Four established ovarian cancer cell lines were evaluated. The patterns of COUP-TF expression were compared to the staining intensities of immunocytochemical assays for estrogen receptor (ER), androgen receptor (AR), aromatase, and HER2/neu. A comparison of the ovarian cancer cell lines showed differential expression of COUP-TF in the nucleus. The pattern of COUP-TF expression did not follow the profile of any of the other four variables. In agreement with transfection experiments showing reduction of activity of other steroid receptors by elevated COUP-TF levels, high COUP-TF expression correlated with low ER activity also in native ovarian cancer cells. These data represent the first reported evidence that COUP-TF-like proteins may play a role in the metabolism and possibly in the process of dedifferentiation of human ovarian cancer.

Aromatase↗
PubMed1979

[Transfer factor (TF) treatment of patients with HBs-Ag-positive chronic active hepatitis. A prospective, controlled study (author's transl)].

It is a clinically and experimentally well supported working hypothesis that infection with hepatitis B virus may result in chronic active hepatitis in patients with suspected immune deficiencies. On this basis, a pilot study was performed in order to evaluate the effect of "specific" transfer factor (TF) in the treatment of HBS-Ag-positive chronic active hepatitis. From the leukocytes of 500 ml venous blood each of 40 volunteers that had completely recovered from acute virus hepatitis B within the last 6 months, a unique TF pool (40 units of TF) was prepared according to the method of Lawrence. Preexaminations indicated that this preparation was able to enhance cellular immune reactions in vitro. Thirteen patients with HBS-antigenemia and chronic active hepatitis (i.e., two liver biopsies within the last 6 or more months with the histological criteria of chronic aggressive hepatitis according to de Groote, elevated serum levels of bilirubin, alkaline phosphatase, transaminase activities, and/or gamma-globulines) were randomized: Seven received s.c. injections of two units of TF each on days 1 and 15, the other six saline. Conversion of skin reactions to some ubiquitous antigens occurred in the TF group, but no significant and constant drop of HBS-Ag serum titers was observed. Although some of the biochemical parameters seemed to ameliorate in the TF group, the differences versus the control group did not prove to be significant within the limited number of patients under observation. The in vitro reactivity of patients' lymphocytes to HBS-Ag, tested by means of the 3H-thymidine uptake, was never found enhanced after TF application. In the used doses, "specific" TF was not effective in the treatment of HBS-Ag-positive chronic active hepatitis; unfavorable side-effects were not observed.

Adult↗
PubMed1995

Immunogenicity of synthetic TF-KLH (keyhole limpet hemocyanin) and sTn-KLH conjugates in colorectal carcinoma patients.

Mucins of colorectal carcinomas overexpress the cancer-associated disaccharides Thomsen-Friedenreich antigen (TF) and sialyl-Tn antigen (sTn), making these antigens suitable for active specific immunotherapy. Patients at high risk for recurrent colon cancer, but free from disease after surgical resection, were immunized with synthetic TF and sTn covalently attached by a two-carbon crotyl linker to keyhole limpet hemocyanin (KLH). Four groups of patients were treated with TF-KLH without adjuvant, TF-KLH plus the immunological adjuvant Detox, sTn-KLH plus Detox, or sTn-KLH plus the immunological adjuvant QS-21, and the serological response was monitored. Enzyme-linked immunosorbent assay (ELISA), dot-blot immunostains, and inhibition assays were used to identify antibody responses against synthetic TF and sTn epitopes and against natural antigens, including asialoglycophorin expressing TF antigen, and ovine submaxillary mucin and the human colon cancer line LS-C expressing sTn antigen. Our results demonstrate that vaccines containing TF or sTn-KLH conjugates plus immunological adjuvants Detox and especially QS-21 induced high IgM and IgG antibody titers against the respective synthetic disaccharide epitopes. However, when tested against natural antigens expressing these disaccharide epitopes, IgM antibodies showed weak to moderate reactivity, while IgG antibodies were almost totally unreactive. On the basis of these results we are continuing to test modifications of synthetic TF and sTn epitopes to identify those that induce IgM and IgG antibodies that are more reactive with these antigens as they are expressed on tumor mucins.

Antibodies, Neoplasm↗
PubMed1995

Localization of transcripts of the related nuclear orphan receptors COUP-TF I and ARP-1 in the adult mouse brain.

The chicken ovalbumin upstream promoter transcription factor, COUP-TF I, and the protein ARP-1 (COUP-TF II) are two highly homologous orphan receptors of the nuclear hormone receptor family. In this study we investigated their expression patterns in the adult nervous system of the mouse. In situ hybridizations were performed on brain sections with 35S-labeled cRNA probes derived from the 3'-non-coding regions of the mARP-1 and mCOUP-TF I mRNAs. Both COUP-TF I and ARP-1 were shown to be expressed in the adult brain and they displayed restricted and distinct expression patterns. COUP-TF I transcripts were predominantly found in the rostral and caudal parts of the adult mouse brain, whereas ARP-1 transcripts prevaled in the middle part of the brain. High expression of COUP-TF I was detected in the olfactory nucleus, in neocortex layers I/II and V/VL, in the dentate gyrus and in areas CA1/CA3/CA4 of the hippocampus, and in the granular layer of the cerebellum. Only low amounts of COUP-TF I mRNA were detected in the ventral, the laterodorsal and in the interanteromedial thalamic nuclei. Small amounts of COUP-TF I transcripts were also found in the epithelial layer of the ventricle and in arachnoid membranes. High expression of ARP-I was detected in the reticular, the ventral lateral and the gelatinosus thalamic nuclei. Other hot spots of ARP-1 mRNA expression were the amygdaloid nucleus and the arachnoid membranes. Lower amounts of ARP-1 transcripts were found in the anterior and lateral hypothalamic areas, in the suprachiasmatic nucleus, and in the choroid plexus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

Isolation, characterization and implications of anti-TF (Thomsen-Friedenreich) agglutinins from different sources.

Anti-TF agglutinins from peanut (Arachis hypogaea) and from vertebrate sera of different species have been successfully isolated by affinity chromatography on acid-activated Sepharose 4 B. The proteins were characterized by immunoelectrophoresis, polyacrylamide gel electrophoresis in the presence of SDS and with respect to their carbohydrate binding specificities. Anti-TF substances from sera showed one precipitin arc in immunoelectrophoresis, but quantitative immunoprecipitation revealed our human anti-TF to be a mixture of the three Ig-classes IgG, IgA and IgM. This finding was confirmed on SDS gel electrophoresis, where high molecular weight aggregates were found before reduction. Hemagglutination inhibition revealed that all isolated anti-TF compounds exhibit an exceptionally high affinity for the immunodominant group of the TF-antigen, namely the beta-D-galactosyl-(1 leads to 3)-N-acetyl-D-galactosamine disaccharide. On examination of formalin-fixed and neuraminidase treated tissue sections (kidney, mammary gland), fluorescein-labelled anti-TF from horse serum showed a virtually identical pattern when compared with fluorescein labelled peanut lectin. Likewise isolated IgA-class myeloma J 539, which shows specificity against beta-(1 leads to 6)-galactans, only bound to the appropriate Gal-beta-(1 leads to 6)-Gal structures, such as those found on bovine lung or the albumin gland of Helix pomatia. Rabbit anti-VCN (Vibrio cholerae neuraminidase) activity could be selectively abolished by beta-galactosyl-containing inhibitors, whereas papain F(ab) fragments from rabbit anti-VCN immunoglobulin did not compete with anti-TF for binding sites on VCN-treated human red cells. Anti-TF, on the other hand, did not compete with anti-VCN for active VCN.

Agglutinins↗
PubMed1982

Distribution of six TF C (transferrin) subtypes in cord bloods and blood donors.

Isoelectric focusing was used to subtype the common TF C phenotype into C1, C2 and C3, increasing the proportion of heterozygotes from virtually zero to 0.31. Five of the six subtypes of TF C were found in a series of 200 blood donors and 200 cord bloods. The frequencies of the three alleles were: TF*C1 = 0.80, TF*C2 = 0.17 and TF*C3 = 0.03 from cord bloods; and TF*C1 = 0.84, TF*C2 = 0.13 and TF*C3 = 0.03 from blood donors. These frequencies were comparable with estimates from other Caucasian populations. The average probability of detecting non-paternity for this population is increased to 11% by subtyping C into C1 and C2, and further increased to 15% by subtyping C into C1, C2 and C3.

Alleles↗
PubMed1997

Modulation of retinoic acid sensitivity in lung cancer cells through dynamic balance of orphan receptors nur77 and COUP-TF and their heterodimerization.

The diverse function of retinoic acid (RA) is mediated by its nuclear receptors, the retinoic acid receptors (RARs) and retinoid X receptors (RXRs). However, the RA response is often lost in cancer cells that express the receptors. Previously, it was demonstrated that the RA response is regulated by the COUP-TF orphan receptors. Here, we present evidence that nur77, another orphan receptor whose expression is highly induced by phorbol esters and growth factors, is involved in modulation of the RA response. Expression of nur77 enhances ligand-independent transactivation of RA response elements (RAREs) and desensitizes their RA responsiveness. Conversely, expression of COUP-TF sensitizes RA responsiveness of RAREs by repressing their basal transactivation activity. Unlike the effect of COUP-TFs, the function of nur77 does not require direct binding of nur77 to the RAREs, but is through interaction between nur77 and COUP-TFs. The interaction occurs in solution and results in inhibition of COUP-TF RARE binding and transcriptional activity. Unlike other nuclear receptors, a large portion of the carboxy-terminal end of nur77 is not required for its interaction with COUP-TF. In human lung cancer cell lines, COUP-TF is highly expressed in RA-sensitive cell lines while nur77 expression is associated with RA resistance. Stable expression of COUP-TF in nur77-positive, RA-resistant lung cancer cells enhances the inducibility of RARbeta gene expression and growth inhibition by RA. These observations demonstrate that a dynamic equilibrium between orphan receptors nur77 and COUP-TF, through their heterodimerization that regulates COUP-TF RARE binding, is critical for RA responsiveness of human lung cancer cells.

Animals↗
PubMed1993

In situ hybridization mapping and restriction fragment length polymorphism analysis of the porcine albumin (ALB) and transferrin (TF) genes.

In situ hybridization analyses were conducted on porcine metaphase chromosomes using porcine liver albumin (ALB) and transferrin (TF) cDNA probes. The ALB gene was assigned to the q12 band of chromosome 8 and the TF gene to the q31 band of chromosome 13. For the latter, a statistically significant secondary peak was observed on the 6p15 band. However, the TF probe predominantly hybridized to the 13q31 band, indicating that this band is the most likely site of the TF gene. Since the TF gene belongs to linkage group V, this linkage group can now be assigned to chromosome 13. The TF and ALB probes were also used for restriction fragment length polymorphism (RFLP) analysis. A screening of 10 unrelated animals revealed TaqI RFLPs for both ALB and TF. Family studies indicated that the ALB and TF polymorphisms were controlled by three and two alleles, respectively.

Alleles↗
PubMed1996

Molecular mechanisms of COUP-TF-mediated transcriptional repression: evidence for transrepression and active repression.

COUP-TF, an orphan member of the nuclear receptor superfamily, has been proposed to play a key role in regulating organogenesis, neurogenesis, and cellular differentiation during embryonic development. Since heterodimierization is a common theme within the nuclear receptor superfamily and has been demonstrated to modulate transcriptional properties of heterodimeric partners via allosteric interactions, we have devised a strategy to examine the silencing function of COUP-TF in a heterodimeric context. We find that the intrinsic active repression function of COUP-TF is not affected by heterodimerization. Moreover, COUP-TF can transrepress the ligand-dependent activation of its heterodimeric partners without its own DNA binding site. Using receptor deletion mutants in transfection assays, we show that the region necessary for COUP-TF silencing function is not sufficient for its transrepression activity. Furthermore, our studies indicate that in addition to its active repression function, COUP-TF can repress several different types of activator-dependent transactivation. However, this active repression function of COUP-TF may be differentially regulated by some other activator(s). These studies provide new insights into the molecular mechanism(s) of COUP-TF-mediated repression.

Allosteric Regulation↗
PubMed1994

Measurement of cytosolic free calcium in perfused rat heart using TF-BAPTA.

The feasibility and usefulness of loading 1,2-bis(2-amino-5,6-difluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (TF-BAPTA), a new high-dissociation constant (KD) (65 microM) Ca2+ indicator, into perfused rat heart is demonstrated. TF-BAPTA-loaded perfused rat heart showed less than a 10% reduction in left ventricular developed pressure. In addition, loading perfused rat heart with TF-BAPTA had no effect on cell high-energy phosphates measured by 31P-nuclear magnetic resonance (NMR). Cytosolic free Ca2+ (Ca2+i) can be monitored in TF-BAPTA-loaded perfused rat heart using 19F-NMR. TF-BAPTA has a Ca(2+)-insensitive resonance (6F) and a Ca(2+)-sensitive fluorine (5F) that responds to changes in Ca2+ binding with fast exchange kinetics at magnetic fields < or = 8.5 T. Thus the shift difference between the 5F and 6F resonances is a measure of Ca2+i. Given the high KD and the slight differences in intra- vs. extracellular fluorine shifts, TF-BAPTA is not well suited for measuring basal Ca2+i, but it is useful for measuring increases in Ca2+i above this level. For studies in which intracellular pH changes are significant, e.g., during ischemia, pH-dependent corrections must be made to obtain an accurate Ca2+i value. Given its fast exchange kinetics, TF-BAPTA is also useful for measurement of free Ca2+ in different compartments or cells with different Ca2+i. We show that the rise in Ca2+i is not uniform during prolonged global ischemia (60 min); several different Ca2+i values are present. Thus TF-BAPTA is a useful new indicator for measuring elevations in Ca2+i or compartmentation of Ca2+i.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

[Molecular cloning, expression and characterization of the clones encoding soluble TF mutants].

Tissue factor (TF) plays an important role in the pathogenesis of atherosclerotic, sepsis and disseminated intravascular coagulation (DIC). TF pathway is therefore an attractive therapeutic target in a number of disease states. Here two TF mutants were developed and named MCsTF and MFsTF, in which the amino acids of active sites were mutated. Both of them were expressed in E.coli and used to inhibit TF pathway through competitive FVII/VIIa binding with TF. The results indicated that rMCsTF almost lost all activities of FX activation and procoagulation, and rMFsTF lost 90% activity. The specific catalytic constant ( k ( cat )/ K (m)) of FX activation by the complex formed by FVIIa with rMCsTF or rMFsTF were 2.0% and 3.7%, respectively, compared to that of rsTF. The inhibition effects of the mutants were studied in vitro, and it appeared that the prothrombin time were prolonged in a dose-dependent manner. Therefore, these mutants of TF may become new kind of specific inhibitors of TF pathway, as a promising drug for the treatment of patients with over-expression of TF.

Arteriosclerosis↗
PubMed1995

Distinction between gamma c detection and function in YT lymphoid cells and in the granulocyte-macrophage colony-stimulating factor-responsive human myeloid cell line, Tf-1.

Peripheral blood monocytes respond to interleukin-2 (lL-2) and express the gamma common (gamma c) subunit of the lL-2 receptor (lL-2R) complex. However, the role of lL-2 in myeloid development has recently become of interest for several reasons, including the effect gamma c mutations may or may not have on myeloid development in patients with XSCID. Many studies of lL-2 function in the myeloid cell lineage have been performed on a murine background. To study gamma c expression and function in human myeloid precursors, we introduced the human myelomonocytic cell line, Tf-1, with a retroviral vector containing the human lL-2R beta subunit to create functional human intermediate lL-2R consisting of beta gamma c dimers. We have characterized this transfected variant of Tf-1 (Tf-1 beta) with regard to its response to lL-2. Unlike the parental Tf-1 cell line that is deficient in both lL-2R alpha and lL-2R beta expression, the Tf-1 beta transfectant binds and responds to lL-2 through intermediate-affinity lL-2Rs. Scatchard analyses indicate the number of intermediate-affinity receptors on Tf-1 beta is similar to the number found on the well-characterized YT cell line. However, detection of gamma c on Tf-1 beta cells is dramatically less than on YT cells by Western blot analysis and is undetectable by flow cytometric studies and surface iodinations. The gamma c component on YT cells is readily detected by all three methods. We conclude from these studies that the intermediate-affinity lL-2Rs on the Tf-1 cell line behave differently than those on YT cells with respect to gamma c detection. Either the gamma c molecule itself is different, or the cellular environment in which it functions is altered. Elucidation of gamma c function on this cell line will allow for its use as a model in which other cytokines using gamma c (including lL-2, lL-4, and lL-15) can be studied on the same cellular background.

Animals↗