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PubMed1979

Restricted chimerism of peripheral blood cells after transplantation of allogeneic hemopoietic tissue in rabbits.

Allogeneic bone marrow or spleen cells were transplanted in rabbits treated with a single dose of 110 kmg/g of cyclophosphamide or four doses of 50 mg/kg. Chimerism of peripheral blood cells occurred in about 50% of the recipients, lasting from about the 14th day until 180 days after transplantation. The chimerism was limited to some kinds of cells since dissociation of proliferation of hemopoietic cells and split chimerism of lymphocytes were observed. Dissociation of proliferation of hemopoietic cells consisted in the appearance of only one cell line, namely lymphocytes, whereas the erythrocyte cells did not proliferate. Split chimerism occurred within lymphocytes, manifested by the presence of the donor's T lymphocytes but absence of proliferation of the donor's B lymphocytes.

Animals↗
PubMed1982

Suppressor cells in transplantation tolerance. II. Identification and probable mode of action of chimeric suppressor T cells.

In order to differentiate between donor (chimeric F1) cells and host cells as being responsible for suppression in transplantation tolerance (TT), cells from tolerant donors were first subject to negative selection through F1 hybrid intermediate host animals. This revealed that the suppressor cells was neither completely removed from the lymph nor recoverable from the lymphoid tissues of the filter rat when highly suppressive inocula were used, suggesting that suppression did not directly depend on cells with receptors for alloantigens. The phenotype of donor and host cells in the recirculating pool was studied with fluorescent antisera and showed that both host cells and chimeric F1 cells were in the thoracic duct lymph of tolerant rats and were capable of recirculation. T and B lymphocytes of both types were present but the IgG-positive, presumptive memory B cells were highly enriched in those rapidly recirculating cells, obtained by filtration of tolerant inocula through irradiated intermediate hosts. These cells were also highly enriched for suppressor function. Methods which selectively depleted either the chimeric T cells or the B cells were applied to tolerant inocula and on adoptive transfer of these inocula, suppression was eliminated only when chimeric T cells were eliminated. This strict dependence of suppression of F1 hybrid T cells is interpreted as evidence that these cells probably suppress directly, via an anti-idiotypic mechanism, the alloreactive cells bearing idiotype-positive major histocompatibility complex receptors.

Animals↗
PubMed1984

Influence of radiation field and fractionation schedule of total lymphoid irradiation (TLI) on the induction of suppressor cells and stable chimerism after bone marrow transplantation in mice.

When BALB/c mice received 17 daily fractions of 2 Gy each of total lymphoid irradiation (TLI, total dose 34 Gy) and 30 X 10(6) C57 B1 bone marrow cells (BM) on the day after the last fraction, stable bone marrow chimerism without signs of graft-vs-host disease (GVHD) was obtained in 84% of the animals. On the contrary, in BALB/c mice receiving only seven fractions of TLI (total dose 14 Gy), all bone marrow grafts were rejected. When the last two fractions of a 14-Gy TLI course were given without shielding the extra lymphatic tissues (combined total lymphoid + total body irradiation, TLBI), chimerism could be induced in 53% of the animals. When this 14-Gy TLBI schedule was used, it was even possible to administer four fractions per day (multiple fractions per day schedule, MFD), thus reducing the overall treatment time to 2 consecutive days. After this concentrated form of TLBI, chimerism was detected in 35% of the animals. As in the 34-Gy TLI schedule, graft-vs-host reaction could not be prevented in the 14-Gy TLBI schedule when spleen lymphocytes (10 X 10(6) were added to the BM inoculum. Leucopenia or suppression of the phytohaemagglutinin (PHA)-induced blastogenesis could not predict which schedule would result in a successful allogeneic bone marrow take. Suppressor cells of the mixed lymphocyte reaction, on the other hand, were only found in the spleen of BALB/c mice treated with the TLI or TLBI schedules, which also resulted in stable bone marrow chimerism.

Animals↗
PubMedDate not supplied

[Chimeric toxin of the A-subunit of viscumin and the B-subunit of ricin].

A chimeric toxic protein was prepared from the mistletoe lectin I A-chain and ricin B-chain by using the disulfide exchange reaction. Ricin and chimeric protein were indistinguishable in binding to immobilized asialofetuin in ELISA. The chimeric protein was more toxic for Jurkat cells than native mistletoe lectin I, but not as effective as native ricin. In the presence of NH4Cl, which enhances the toxicity of some toxins and immunotoxins, but does not influence ricin toxicity, both ricin and chimeric toxin had equal cytotoxic activity. The possibility is discussed that the ricin B-chain protects the ricin A-chain from degradation during delivery from the cell surface to the place where it is translocated into the cytosol.

Asialoglycoproteins↗
PubMed1995

A novel bifunctional chimeric complement inhibitor that regulates C3 convertase and formation of the membrane attack complex.

Human cells express cell surface complement regulatory molecules that inhibit the activity of the C3/C5 convertases (DAF, MCP, CR1) or inhibit the membrane attack complex (CD59). A single molecule that inhibits both the convertase activity and formation of the membrane attack complex has never been characterized. To this end, we have developed two reciprocal chimeric complement inhibitors (CD, NH2-CD59-DAF-GPI; and DC, NH2-DAF-CD59-GPI) that contain the functional domains of decay accelerating factor (DAF; CD55) and CD59. Cell surface expression of the CD and DC chimeric proteins was detected with DAF- and CD59-specific antisera. Cell surface C3d deposition was inhibited on cells expressing the chimeric molecules, thereby indicating that the DAF moiety was functional in both molecules. Conversely, Ab-blocking experiments demonstrated that only the DC molecule retained CD59 function. Therefore, the DC molecule represents a novel potent chimeric bifunctional complement inhibitor that retains the functional domains of two distinct complement regulatory molecules.

Animals↗
PubMed1993

Conformational influence of the ribose 2'-hydroxyl group: crystal structures of DNA-RNA chimeric duplexes.

We have crystallized three double-helical DNA-RNA chimeric duplexes and determined their structures by X-ray crystallography at resolutions between 2 and 2.25 A. The two self-complementary duplexes [r(G)d(CGTATACGC)]2 and [d(GCGT)r(A)d(TACGC)]2, as well as the Okazaki fragment d(GGGTATACGC).r(GCG)d(TATACCC), were found to adopt A-type conformations. The crystal structures are non-isomorphous, and the crystallographic environments for the three chimeras are different. A number of intramolecular interactions of the ribose 2'-hydroxyl groups contribute to the stabilization of the A-conformation. Hydrogen bonds between 2'-hydroxyls and 5'-oxygens or phosphate oxygens, in addition to the previously observed hydrogen bonds to 1'-oxygens of adjacent riboses and deoxyriboses, are observed in the DNA-RNA chimeric duplexes. The crystalline chimeric duplexes do not show a transition between the DNA A- and B-conformations. CD spectra suggest that the Okazaki fragment assumes an A-conformation in solution as well. In this molecule the three RNA residues may therefore lock the complete decamer in the A-conformation. Crystals of an all-DNA strand with the same sequence as the self-complementary chimeras show a morphology which is different from those of the chimera crystals. Moreover, the oligonucleotide does not match any of the sequence characteristics of DNAs usually adopting the A-conformation in the crystalline state (e.g., octamers with short alternating stretches of purines and pyrimidines). In DNA-RNA chimeric duplexes, it is therefore possible that a single RNA residue can drive the conformational equilibrium toward the A-conformation.

Base Sequence↗
PubMed1993

Persistence of human multilineage, self-renewing lymphohematopoietic stem cells in chimeric sheep.

We have previously reported the ability of uncharacterized human bone marrow (BM) cells to engraft into preimmune fetal sheep, thereby creating sheep-human chimera suitable for in vivo examination of the properties of human hematopoietic stem cells (HSC). Adult human bone marrow CD34+ HLA-DR- cells have been extensively characterized in vitro and have been demonstrated to contain a number of primitive hematopoietic progenitor cells (PHPC). However, the capacity of such highly purified populations of human marrow CD34+ HLA-DR- cells to undergo in vivo self-renewal and multipotential lymphohematopoietic differentiation has not been previously demonstrated. To achieve that, human CD34+ HLA-DR- cells were transplanted in utero into immunoincompetent fetal sheep to investigate the BM-populating potential of these cells. Long-term chimerism, sustained human hematopoiesis, and expression of human cells belonging to all human blood cell lineages were demonstrated in two animals for more than 7 months' posttransplantation. Chimeric BM contained erythroid, granulocytic/monocytic, and megakaryocytic hematopoietic progenitor cells, as well as the primitive high proliferative potential colony-forming cell (HPP-CFC). Under a variety of in vitro experimental conditions, chimeric BM cells gave rise to human T cells expressing T-lymphocyte-specific markers, human natural killer (NK) cells, and human IgG-producing B cells. In vivo expansion and possibly self-renewal of transplanted PHPC was confirmed by the detection in chimeric BM 130 days' posttransplantation of CD34+ HLA-DR- cells, the phenotype of human cells constituting the stem-cell graft. These studies demonstrate not only the BM-populating capacity, multipotential differentiation, and most likely self-renewal capabilities of human CD34+ HLA-DR- cells, but also that this BM population contains human HSC. Furthermore, it appears that this animal model of xenogeneic stem-cell transplantation is extremely useful for in vivo examination of human hematopoiesis and the behavioral and functional characteristics of human HSC.

Animals↗
PubMedDate not supplied

Active cross-protection induced by a recombinant baculovirus expressing chimeric infectious bursal disease virus structural proteins.

The VP2 structural gene encoded in the large genomic segment A of the variant GLS strain of infectious bursal disease virus (IBDV) was modified to encode a neutralization epitope (B69), found only on classic strains of IBDV. A chimeric cDNA clone of the large segment A, encoding VP3, VP4, and the modified variant IBDV VP2 structural proteins, was expressed in a recombinant baculovirus. The chimeric protein expressed was assessed with a panel of neutralizing monoclonal antibodies (MAbs), and it contained not only all previously MAb-defined GLS variant strain epitopes but also the B69 neutralization epitope found on classic IBDV strains. Complete active protection was afforded to specific-pathogen-free chickens by a subunit chimeric vaccine against virulent challenge with the classic IM and STC strains, as well as against the variant E/Del and GLS IBDV strains. Compared with a previously tested recombinant subunit vaccine, which incorporated unmodified baculovirus-expressed large-segment A GLS proteins, the recombinant chimeric subunit vaccine resulted in markedly improved active cross-protection against classic IBDV challenge.

Animals↗
PubMed1995

Detection of mixed chimerism and leukemic relapse after allogeneic bone marrow transplantation in subpopulations of leucocytes by fluorescent in situ hybridization in combination with the simultaneous immunophenotypic analysis of interphase cells.

Serial blood and marrow specimens from eight adult recipients of sex-mismatched transplants (BMT) for chronic myeloid leukemia (CML, n = 3), Ewing sarcoma (n = 1), acute myeloid leukemia (AML) in second remission (n = 1), acute lymphatic leukemia (ALL, n = 1) and multiple myeloma (n = 2) were analyzed by the simultaneous immunophenotypic CD3, CD4, CD8, CD20, CD34, CD10 and genotypic analysis (for X and Y chromosomes). This combined technique of moAb/APAAP staining for cell surface and cytoplasmic antigens and fluorescence in situ hybridization (FISH) for the detection of sex chromosomes allowed the qualitative and quantitative evaluation of mixed chimerism and/or relapse. Using the same slides for moAb/APAAP and FISH allowed the simultaneous identification of the cell lineage, the lymphocyte subpopulation and the genotype (XX or YX) in every blood or BM specimen analyzed. A mixed chimerism in the T cell (CD4, CD8+: median 26% host cells, range 5-44%) and in the myelomonocytic cell population (CD14+ median 16% host cells, range 5-50%) was observed at day +7 after BMT. By days +14 to +18 this mixed chimerism was reduced to 18% host T cells (range 5-50%) and 7% host myelomonocytic cells (range 0-20%). Beyond days +21 to +28 a stable donor chimerism for T cells, myelomonocytic cells and granulocytes was observed in seven of eight patients. Still 0.5-1% host cells of different lineages were detectable in five from the eight patients at later time points (> day + 100). In three patients with CML these cells were CD13 or CD13, CD34 positive and in one was CD4, CD8 positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Mixed allogeneic chimerism and renal allograft tolerance in cynomolgus monkeys.

We have developed a nonmyeloablative preparative regimen that can produce mixed chimerism and renal allograft tolerance between MHC-disparate nonhuman primates. The basic regimen includes ATG, nonmyeloablative total-body irradiation (TBI, 300 rads), thymic irradiation (TI, 700 rads), and donor bone marrow infusion. Kidney allografts from MHC-mismatched donors were transplanted with various manipulations of the preparative regimen. Monkeys treated with the basic regimen alone (n = 2) rejected allografts by day 15. With the addition of cyclosporine (CsA) for one month (n = 3), one monkey developed multilineage mixed chimerism and renal allograft tolerance thereafter (> 430 days). To reduce the toxicity of the preparative regimen, TBI was fractionated to 150 rads on two successive days in subsequent studies. All monkeys receiving this modified regimen (n = 4) developed multilineage chimerism with fewer side effects and accepted renal allografts long-term with no further immunosuppression (196 days, 198 days, > 150 days, and > 40 days). In long-term survivors, donor-specific nonreactivity was confirmed by MLR and skin transplantation. Three monkeys treated with the basic regimen plus CsA but with only 150 rads of TBI (n = 1) or no TBI (n = 2) did not develop multilineage chimerism and grafts were rejected (day 40-50) soon after the CsA discontinuation. Monkeys treated with the same regimen, but without DBM (n = 2), rejected kidney allografts by day 52. Therefore, at least transient engraftment of DBM appears to be essential for induction of donor specific tolerance in this monkey model.

Animals↗
PubMed1994

Construction and characterization of chimeric and humanized forms of a broadly neutralizing monoclonal antibody to HIV-1.

Murine monoclonal antibody (MAb) G3-519 has been shown to recognize a conserved neutralizing epitope in the fourth constant (C4) region of the external glycoprotein gp120 of HIV-1. Inasmuch as this antibody effectively neutralized the infectivity of diverse HIV-1 isolates, it has been selected to be developed for passive immunization against HIV-1 infection in humans. In order to minimize the problem of immunogenicity of murine antibodies and to confer additional accessory immune functions, we have constructed mouse/human chimeric and humanized forms of the antibody. The chimeric antibody was constructed by cloning the murine variable regions and replacing the mouse constant regions with those from human Ig gamma 1,kappa. The humanized antibody was constructed using the human KAS variable region framework sequences as template. Engineering was guided by a three dimensional model of the murine variable region. The murine, chimeric and humanized forms of the antibody exhibited similar reactivity with the peptidic antigen in ELISA, and comparably neutralized the infectivity of HIV-1 in vitro. Taken together, our results show that the chimeric and humanized forms of G3-519 essentially retain the binding activity of the mouse parental antibody. Clinical development is planned to assess the prophylactic and therapeutic usefulness of these reshaped antibodies in humans.

Amino Acid Sequence↗
PubMed1995

Radiolabeled chimeric anti-CEA monoclonal antibody compared with the original mouse monoclonal antibody for surgically treated colorectal carcinoma.

UNLABELLED: Biodistribution and tumor uptake of a chimeric human-mouse monoclonal antibody (MAb) and the original mouse MAb have been comparatively studied. METHODS: Eighteen patients with suspected colorectal cancer scheduled for surgery underwent immunoscintigraphy with 123I-labeled chimeric anti-CEA MAb. Iodine-125 and 131I trace-labeled chimeric and original mouse MAb were simultaneously injected for biodistribution studies. RESULTS: Similar serum kinetics and a low immunogenicity were observed for both antibodies. Mean binding capacity to CEA measured in PBS after radiolabeling was identical for both MAbs and it was slightly decreased when measured in serum 1-4 hr after injection. Radiochromatograms of patients sera showed immune complex formation related to the amount of circulating CEA. Postoperative ex vivo radioactivity counting in tissue samples revealed similar antibody distributions with notably similar antibody uptakes in tumors. High tumor uptakes (between 0.02 to 0.06% injected dose per g) were observed in 3 of 13 patients operated for primary or metastatic colorectal cancer. CONCLUSION: In this dual-label technique, the radioiodinated anti-CEA IgG4 chimeric MAb and the original mouse IgG1 MAb were shown to have very similar behavior in colorectal cancer patients.

Adult↗
PubMed1993

[Successful prevention of rhinovirus infections with chimeric ICAM-1 immunoglobulin in vitro].

The intercellular adhesion molecule 1 (ICAM-1) is used as cellular receptor by 90% of human rhinoviruses (HRV). Recently, a recombinant, soluble ICAM-1 (sICAM-1) has been shown to be effective in prevention of the cytopathic effect of rhinovirus infection in vitro. Aim of this study was the production of molecules with multivalent binding sites. Different chimeric proteins were constructed by fusion of two or five extracellular domains of ICAM-1 with the constant regions of IgA1, IgM and IgG1 by polymerase chain reactions (PCR). IgA- and IgG-immunoadhesion molecules were expressed in eucaryotic cells as dimers, IgM-immunoadhesion molecules as decamers. Immunoadhesion molecules were compared to sICAM-1 for their ability to neutralize HRV: The chimeric protein of five N-terminal domains of ICAM-1 and the constant regions of IgA1 was 150 times more potent than sICAM-1 in neutralizing HRV. The first and the second N-terminal of ICAM-1 fused to IgA1 or IgM were five times more active, however, fused to IgG1 four times less active than sICAM-1. Sedimentation analyses of [H3]-leucin labled HRV after preincubation with the different immunoadhesion molecules showed a dose-dependent induction of a conformational change of the viral capsid proteins. The order of efficiency of the chimeric proteins was consistent to the neutralizing experiments. Our results showed that HRV neutralizing can be dramatically increased by multimerization of ICAM-1. The chimeric molecule between IgA1 and ICAM-1 seems to be a potential candidate for clinical testing to prevent and treat HRV-infections.

Cell Adhesion Molecules↗
PubMed1994

Stable multilineage hematopoietic chimerism in alpha-thalassemic mice induced by a bone marrow subpopulation that excludes the majority of day-12 spleen colony-forming units.

We have investigated the contribution of highly purified day-12 spleen colony-forming units (CFU-S-12) as well as more primitive cells to sustained blood cell production using in vivo and in vitro assays that allow frequency analysis. Normal or day-6 post-5-fluorouracil light-density bone marrow (BM) was sorted on the basis of differences in rhodamine-123 (Rh123) retention or wheat germ agglutinin (WGA) affinity and tested in vivo using a recently developed alpha-thalassemic chimeric mouse model. In addition, short-term and long-term clonal activity was assessed in vitro using a limiting dilution-type long-term BM culture, the cobblestone area forming cell assay. When sublethally irradiated alpha-thalassemic mice were transplanted with as many as 281 purified WGAbright CFU-S-12, derived from a fraction containing 95% of all CFU-S-12 from day-6 post-5-fluorouracil light-density BM of wild-type mice, detectable chimerism was not observed at 6 months posttransplantation. In contrast, only three CFU-S-12 were included in the Rh123dull and WGAdim subpopulations that induced 29% to 58% and 21% to 31% stable multilineage donor-type chimerism of erythrocytes and leukocytes, respectively. The Rh123dull and WGAdim cells were up to 240-fold enriched for long-term repopulating ability (LTRA) as compared with unseparated BM. A comparable level of chimerism was found in the different hematopoietic organs and at the level of BM CFU-S-12. The frequency of the LTRA unit capable of inducing a 10% sustained level of donor-type erythrocytes was calculated to be 1 to 2 per 10(5) BM cells. Several reports have suggested that LTRA and spleen colony formation could be capacities of the same stem cell subset. However, the present results show that the majority of CFU-S-12 have only short-term repopulating ability and are physically separable from more primitive stem cells with long-term multilineage reconstituting capacities.

Animals↗
PubMed1994

Localization of the ligand binding site of the neurokinin-1 receptor: interpretation of chimeric mutations and single-residue substitutions.

Previous studies have indicated that substitution of the third or fourth extracellular segment of the human neurokinin-1 receptor with the equivalent segment from the neurokinin-3 receptor affects the binding affinities of peptide agonists and/or nonpeptide antagonists. To elucidate the roles of the divergent residues within these domains in ligand binding, single-residue substitutions in these regions were analyzed. Neurokinin B affinity was increased by one single-residue substitution (E172K) in the third extracellular segment and one double-residue replacement (L279R+K280W) in the fourth extracellular segment, and the affinity for the antagonist L-703,606 was reduced by one single-residue substitution (Y272A) in the fourth extracellular segment. The effect of these three specific substitutions is consistent with the prediction of chimeric mutations. However, the substantial reduction in ligand binding affinity observed upon multiple-residue substitutions in the third extracellular segment (residues 176-183 or 187-195) has not been reproduced by eliminating potential electrostatic interactions or substituting with the corresponding residues from the neurokinin-3 receptor, suggesting that the reduction in ligand binding affinity observed with some chimeric receptors is not due to the loss of direct electrostatic interactions. These data indicate that other factors such as conformational effects may complicate the interpretation of data obtained with chimeric receptors, and they demonstrate the need to evaluate chimeric receptors along with single-residue substitutions in the same region to localize specific residues involved in ligand binding. Furthermore, the available data suggest that one major determinant of peptide selectivity in the neurokinin-1 receptor may be the conformational compatibility between a peptide and the receptor.

Amino Acid Sequence↗
PubMed1993

Rhenium-186-labeled chimeric antibody NR-LU-13: pharmacokinetics, biodistribution and immunogenicity relative to murine analog NR-LU-10.

A mouse-human chimeric monoclonal antibody (NR-LU-13), with the same pancarcinoma antigen recognition site as a previously studied murine monoclonal antibody (NR-LU-10), was radiolabeled with 186Re using a bifunctional chelate. Nine patients (ages 31-81 yr) with metastatic adenocarcinoma received 186Re NR-LU-13. A single intravenous dose of 42 mg NR-LU-13 labeled with 25 mCi/m2 (two patients) or 60 mCi/m2 (seven patients) was administered. Mean serum disappearance half-time values for the chimeric 186Re NR-LU-10). Fifty percent of the radiolabel was excreted in the urine by 6 days. Tumor localization was demonstrated by gamma camera imaging in seven of nine patients. The percent injected dose per gram in a single tumor biopsy specimen was 0.003% at 72 hr postinjection. Absorbed dose to bone marrow was 1.5 +/- 0.7 rads/mCi and resulted in reversible myelosuppression in five of six evaluable patients who received 60 mCi/m2: median WBC nadir = 2500/microliters; median platelet nadir = 85,500/microliters. Low grade fever, nausea, slight elevations of liver function tests and mild allergic reactions were seen in some patients. The chimeric antibody elicited low levels of anti-NR-LU-13 antibody in six of eight evaluable patients (75%), in contrast to NR-LU-10 which elicited higher levels of human anti-mouse antibody in all patients. This pilot study demonstrates the ability of the chimeric antibody to target tumors with reduced (but not absent) immunogenicity and delayed clearance relative to the murine antibody.

Adenocarcinoma↗
PubMed1993

Direct localization comparison of murine and chimeric B72.3 antibodies in patients with colon cancer.

To compare radiolocalization of murine B72.3 (m-B72.3) and mouse/human chimeric B72.3 (ch-B72.3) antibodies, five patients with biopsy confirmed adenocarcinoma of the colon received both radiolabeled antibodies 4 or 7 days before laparotomy. Following antibody administration, preoperative gamma camera images showed localization to sites of disease in four of the five patients. Autoradiography of resected specimens showed that both labeled antibodies localized specifically to the tumor with only minimal amounts in normal tissues. Radioactivity from each isotope in biopsy specimens of tumor and normal tissues was quantitated by scintillation gamma counting. Comparison of the percentages of injected activities for each antibody in resected tumor and normal tissue yields tumor to normal tissue radiolocalization ratios of 2.7-13.3 and 0.9-6.3 for murine and chimeric antibodies, respectively. The higher ratios for murine antibody were due to lower normal tissue levels, reflecting its faster clearance from the circulation, whereas the quantitative uptake of labeled antibody was always greater with the chimeric antibody. The chimera to murine antibody ratios in tumor of 1.1-2.7 suggest modest enhancement of tumor localization with chimeric antibody because of its longer half-life.

Aged↗
PubMed1993

Ligand-dependent activation of chimeric receptors with the cytoplasmic domain of the interleukin-3 receptor beta subunit (beta IL3).

beta IL3 (formerly known as AIC2A), a beta subunit of the murine interleukin-3 receptor (IL-3R), is not only required for formation of the high affinity receptor but is also important for signal transduction. To examine the function of beta IL3 in signal transduction, we constructed several chimeric receptors consisting of the intracellular portion of beta IL3 and the extracellular portion of other members of the cytokine receptor superfamily, i.e. the human interleukin-2 receptor beta chain (hIL-2R beta), the human interleukin-4 receptor (hIL-4R), and the murine erythropoietin receptor (mEpoR). These chimeric receptors and normal cytokine receptors were expressed in an IL-3-dependent murine pro-B cell line, Ba/F3, and an IL-2-dependent murine T cell line, CTLL2. Regardless of the origin of the extracellular domain, these chimeric receptors were functional in Ba/F3 cells; they stimulated proliferation and induced tyrosine phosphorylation in response to the cytokine corresponding to the extracellular domain. However, the response of transfectants expressing chimeric receptors was similar to, but not identical with, the response of Ba/F3 cells to mIL-3. We present evidence that the IL-4R and EpoR probably have an additional component which is involved in signal transduction.

Animals↗