Showing papers on "Interferon published in 1980"

Human leukocyte interferon produced by E. coli is biologically active

Abstract: A human leukocyte interferon cDNA was enzymatically synthesized, inserted into the vector pBR322, and cloned in Escherichia coli. The DNA sequence codes for a 23-amino acid signal peptide followed by an interferon polypeptide of 165 amino acids. An expression plasmid was constructed which permits the synthesis in E. coli of 2.5 x 10(8) units of interferon per litre of culture. This LeIF protected squirrel monkeys from lethal encephalomyocarditis virus infection.

Synthesis in E. coli of a polypeptide with human leukocyte interferon activity

Abstract: Double-stranded cDNA prepared from the 12S fraction of poly(A) RNA from interferon (IF)-producing human leukocytes was cloned in Escherichia coli using the pBR322 vector. One of the resulting clones had a 910-base pair insert which could hybridise to IF mRNA and was responsible for the production of a polypeptide with biological IF activity. Up to 10,000 units IF activity per g of cells was obtained from some clones.

Two interferon mRNAs in human fibroblasts: in vitro translation and Escherichia coli cloning studies.

Abstract: Two mRNA species that produce biologically active interferon were isolated from human fibroblasts and studied by size fractionation and cloning in Escherichia coli plasmid pBR322. The major fibroblast interferon (Hu IFN-beta 1) is coded for by the smaller of the two mRNAs, an 11S species, 900 nucleotides long, which in cell-free systems yields a 20,000 Mr protein. The second interferon mRNA species (Hu IFN-beta 2) is 14S, about 1300 nucleotides long, and codes for another protein of 23,000-26,000 Mr. The two interferon mRNAs do not cross-hybridize. Both are induced by poly(rI.rC), but IFN-beta 2 mRNA is induced to about 10% in cells by cycloheximide treatment alone whereas under these conditions IFN-beta 1 is not induced.

Inhibition of cell motility by interferon.

Abstract: Interferon derived from human leukocytes, human fibroblasts, and mouse fibroblasts was found to inhibit the motility of cultured cells. It inhibits the tumor-induced motility of capillary endothelial cells as well as the spontaneous migration of other cell types. The ability of a given preparation of interferon to inhibit the motility of a given cell type is proportional to its antiviral activity in that particular cell type. Antiserum to human leukocyte interferon neutralizes both the motility-inhibitory activity and the antiviral activity of this preparation.

At least three human type alpha interferons: structure of alpha 2

Abstract: The sequence of a human leukocyte-derived complementary DNA (cDNA), Hif-2h, which directs the formation in Escherichia coli of a polypeptide, IFN-alpha 1, with interferon (IFN) activity has been described. A second IFN cDNA, Hif-SN206, which also elicits synthesis of a biologically active IFN, IFN-alpha 2, is described in this article. Whereas IFN-alpha 2 is twice as active on human as on bovine cells, IFN-alpha 1 is 10 to 20 times more active on bovine than on human cells. As deduced from the cDNA's, the messenger RNA's for the two IFN's differ in length and in 20 percent of the nucleotides; the mature IFN polypeptides differ in 17 percent of the amino acids. Both IFN-alpha 1 and IFN-alpha 2 differ from the lymphoblastoid IFN described by others. Therefore, at least three different IFN-alpha genes are expressed in man; studies on genomic DNA reveal the presence of at least eight IFN-related genes.

Differential efficacies of human type I and type II interferons as antiviral and antiproliferative agents.

Abstract: Treatment of human fibroblast FS-4 cultures with human type II interferon preparations induced the synthesis of at least four proteins that were similar in size to four of the five proteins induced by type I interferons (Mr 120,000, 88,000, 67,000, and 56,000). However, the Mr 67,000 and 56,000 proteins were induced more strongly by type II than by type I interferon, and a counterpart of a Mr 80,000 protein induced by type I interferons was not noticeably induced by type II interferon preparations. We therefore compared type I and type II interferons for relative antiviral activities against different viruses (vesicular stomatitis, encephalomyocarditis, and vaccinia viruses and reovirus) and for cell growth-inhibitory activities on various cell types. The replication of vesicular stomatitis and encephalomyocarditis viruses was inhibited more strongly by type I interferon, whereas reovirus and vaccinia virus showed greater sensitivity to type II interferon preparations. This indicates that viruses may differ in their sensitivity to human type I and type II interferons and that the antiviral mechanisms induced by type I and type II interferons may have significant differences. The type I and type II interferons may have significant differences. The type I and type II interferons may also differ in their efficacies as antiproliferative agents. Type II interferon preparations at 2.5 units/ml inhibited the incorporatin of [3H]thymidine to a greater extent than did type I interferon at 400 units/ml. (For both type I and type II interferons, the unit of interferon activity was defined as the concentration that decreased the yield of vesicular stomatitis virus by 50% in FS-4 cultures.) Furthermore, whereas type II interferon preparations had a reversible cytostatic effect on normal human fibroblasts at 10 units/ml, the transformed cells tested (HeLa, osteosarcoma, U-amnion) showed extensive cell death, thus indicating that it may have a cytocidal effect on certain tumor cells. It appears that human type II interferon (or a factor present in these preparations) may be a potent antitumor agent.

High-affinity binding of 125I-labelled mouse interferon to a specific cell surface receptor

Abstract: Previous research suggests that interferon binds to the cell surface, possibly by attachment to gangliosides. A two-component receptor system consisting of binding and activation sites has been proposed. This hypothesis is supported by the finding that interferon inhibits binding of cholera toxin and thyrotropin to their receptors suggesting possible common receptor sites. Moreover, an antiserum against cell surface components of interferon-sensitive cells has been shown to inhibit the action of interferon. However, to understand the interaction of interferon with the cell surface requires direct ligand-binding studies. I present here direct evidence that high-affinity binding of interferon to a specific cell surface receptor is an initial step in interferon action using biologically active purified 125I-labelled mouse interferon. Labelled interferon binds specifically to interferon-sensitive mouse leukaemia L1210 cells, whereas binding to interferon-resistant L1210 cells is nonspecific. Furthermore, specific binding to monolayer cultures of mouse L929 cells is compared with nonspecific binding to chick embryo fibroblasts insensitive to the action of mouse interferon.

A monoclonal antibody for large-scale purification of human leukocyte interferon

Abstract: A clone of hybrid myelomas (NK2), secreting a mouse monoclonal antibody to human leukocyte interferon, has been isolated. The antibody neutralizes the antiviral activity of the interferon and, when covalently attached to a solid support and used as an immunoadsorbent, allows interferon purification of up to 5,000-fold in a single step.

A family of structural genes for human lymphoblastoid (leukocyte-type) interferon.

Abstract: Amino acid sequences of tryptic and chymotryptic peptides from human lymphoblastoid interferon (IFN-alpha) have been determined. The results show that IFN-alpha consists of a family of proteins with at least five different, but homologous, primary structures. There appears to be little, if any, glycosylation of the major components of IFN-alpha.

Deficient natural killer cell activity in x-linked lymphoproliferative syndrome

Abstract: The activity of natural killer cells was found to be deficient in 10 of 12 males with X-linked lymphoproliferative syndrome, a life-threatening proliferation of lymphocytes after infection by Epstein-Barr virus. The activity levels of natural killer cells from affected males were increased after treatment with interferon in vitro, but normal levels of killing were not obtained. Deficient activity of killer cells in individuals with immunodeficiency and chronic infection by Epstein-Barr virus may contribute to the development of lymphoproliferative disorders.

Virus-induced diabetes mellitus. XVIII. Inhibition by a nondiabetogenic variant of encephalomyocarditis virus.

Abstract: Plaque purification of the M variant of encephalomyocarditis (EMC) virus resulted in the isolation of two stable variants: one diabetogenic and designated D and the other nondiabetogenic and designated B. When the D variant was inoculated into SJL/J male mice, hypoinsulinemia and hyperglycemia developed in > 90% of the animals. In contrast, none of the mice inoculated with the B variant developed diabetes. Histologic examination of pancreata from mice infected with the D variant revealed insulitis and necrosis of beta cells, whereas islets from mice infected with the B variant showed little, if any, change. When islets were assayed for infectious virus, approximately 10 times more virus was recovered from animals inoculated with the D as compared with the B variant. Moreover, approximately 60% of islet cells from mice infected with the D variant contained viral antigens when stained with fluorescein-labeled anti-EMC virus antibody, whereas < 5% of islet cells from animals infected with the B variant contained viral antigens. Co-infection experiments showed that the induction of diabetes by the D variant was inhibited by the B variant. When the B and D variants were mixed together at B:D ratios of 1, 9, and 99, diabetes developed in 60, 11, and 0% of the mice, respectively. Tissue-culture experiments revealed that the B variant induced considerably more interferon than the D variant, and studies in animals showed that interferon appeared earlier and in greater amounts in the circulation of mice infected with the B as compared with the D variant. These studies suggest that the induction of interferon by the B variant is, at least in part, responsible for the inhibition of diabetes by the D variant.

Mode of regulation of natural killer cell activity by interferon

Abstract: Whereas xenogeneic tumors such as baby hamster kidney or HeLa cells grow in nude mice, the same cells persistently infected with a variety of viruses are rejected. Spleen cells from normal nude mice were found to be induced to produce interferon and to exert natural killer (NK) activity on virus persistently infected (PI) tumor cells, and not on uninfected parental cells in vitro. The phenotype of the interferon-producing cells and the NK effector cells was found to be the same namely, Qa 5(+), Ly 5(+), ganglio-N- tetraosylceramide, with 35 percent of the NK cells also expressing Thy 1.2. NK activity against virus PI tumor cell lines could be nonspecifically augmented both in vivo and in vitro by prior contact with virus PI tumor cells. It was unambiguously demonstrated with chemically homogeneous mouse interferon that interferon, and not a contaminant, was responsible for the augmentation of NK activity in vitro. Studies on the mode of interferon action in augmenting NK activity revealed that the target cell for interferon action was serologically distinct from the NK effector cell. Anti-Ly 5 + complement (C)-treated spleen cells were depleted of NK activity and the ability to produce interferon, but, upon incubation with interferon for 1-3 h, regained both NK activity and susceptibility to anti-Ly 5 + C. Treatment with anti-Qa 5 + C eliminated NK activity, which could not be restored by the addition of interferon. We conclude that interferon produced by Ly 5(+) cells in response to virus PI tumor cells acts on Ly 5(-) precursor cells and induces their differentiation into functional Ly 5(+) NK effector cells.

In vivo natural reactivity of mice against tumor cells.

Abstract: A rapid in vivo clearance of tumor cells was found in normal mice following intravenous inoculation of [125l]dUrd-labelled YAC-1 and RBL-5 cultured cell lines derived from lymphomas. The ability of mice to eliminate tumor cells from spleen, liver and lungs during the first 4 h, as evaluated by the recovery of radioactivity in these organs, was found to correlate with the level of natural killer (NK) cell reactivity in their spleen and lungs, as measured simultaneously in vitro in a shortterm 51Cr release assay (CRA). Lower recovery of radioactivity was found in mouse strains with high spontaneous levels of NK activity. The degree of clearance was also found to be age-dependent and older mice of several strains, whose NK activity had declined to low levels, were less effective in eliminating tumor cells. In vivo treatment with interferon and interferon inducers (poly I:C, pyran copolymer, Corynebacterium parvum, murine sarcoma virus) increased the levels of NK activity in the spleen and lungs and also augmented the in vivo clearance of tumor cells from the lungs and liver. Immunopharmacological treatments with antimacrophage agents (silica, iota-carrageenan, Seakem-carrageenan), antineoplastic drugs (dexamethasone, cyclophosphamide, 5-(3,-3′dimethyl-I-triazeno)-imidazole-4-carboxamide, 4-amino-L-D-arabinofuranosyl-2-(IH)-pyrimidone, adriamycin) or irradiation (850 R γ-ray) had comparable effects on both in vitro cytolytic activity and in vivo clearance of tumor cells. When the susceptibility to in vitro and in vivocytotoxicity by several other tumors was examined, the lines with detectable sensitivity to lysis by NK cells were found to be cleared in vivo to a greater degree in a high NK strain (CBA) than in a low NK strain (SJL). In contrast, NK-resistant lines were cleared at approximately the same rate in both strains. However, the actual levels of in vivo clearance and the degree of difference between the strains for the various NK-sensitive lines did not correlate well with their relative sensitivities to lysis in vitro. In the various situations in which the in vivo recovery of a particular NK-sensitive line was studied relative to the levels of NK reactivity in the recipients, the best correlations were seen with clearance from the lungs. In several instances, clearance from the spleen did not correlate well with splenic NK activity. These data indicate that rapid in vivo clearance of radiolabelled NK-sensitive tumor cell lines is appreciably influenced by levels of NK reactivity, but that other factors are probably also involved.

Dysfunction of natural killer cells in multiple sclerosis: a possible pathogenetic factor.

Abstract: Natural killer (NK) cell activity, antibody-dependent cytotoxicity (ADCC) and the effect of interferon on NK activity was investigated in multiple sclerosis (MS) patients. NK activity measured against K-562 tumour cell line was found to be significantly low in MS patients, and this was most pronounced in the group of male patients with definitive disease. The response of NK cells to interferon proved to be impaired and almost no activation could be demonstrated in response to polyinosinic-polycytidylic acid (poly I:C). Preliminary data obtained by the determination of interferon production in several definitive MS cases reflect a defect in the interferon producing capacity of lymphocytes. The possible involvement of impaired NK cell function in the aetiopathogenesis of MS is discussed.

Chediak-Higashi gene in humans. I. Impairment of natural - killer function

Abstract: Natural-killer (NK)-cell function was profoundly depressed in donors homozygous for the Chediak-Steinbrinck-Higashi syndrome (C-HS) gene when compared with age- and sex-matched normals. This apparent defect was not simply a result of a delayed response because little cytolysis was evident in kinetics experiments even after 24 h of incubation. NK cells from C-HS donors failed to lyse adherent (MDA, CEM, and Alab) or nonadherent (K562 and Molt-4) tumor cell lines or nontransformed human fetal fibroblasts. Therefore, the apparent C-HS defect was not a result of a shift in target selectivities. In addition, the depressed reactivity did not appear to be a result of suppressor cells or factors because: (a) enriched NK populations (nonadherent lymphocytes bearing receptors for the Fc portion of IgG) from C-HS donors were low in NK-cell function, (b) C-HS mononuclear cells did not inhibit the cytotoxicity of normal cells in coculture experiments, and (c) cells from the C-HS donors remained poorly reactive even after culture for up to 7 d. The nature of the defective NK activity in C-HS patients is not clear but may lie within the lytic mechanism rather than at the level of the recognition structure or population size because the frequency of target-binding cells was normal. In vitro NK activity could be partially restored by interferon treatment. Combined with the results presented in the following paper (4), these observations suggest that the C-HS gene causes a selective immunodeficiency disorder, mainly involving NK cells. This finding, in conjunction with the high incidence of spontaneous possibly malignant, lymphoproliferative disorders in these patients, may have important implications regarding the theory of immune surveillance mediated by NK cells.

Role of G0-G1 arrest in the inhibition of tumor cell growth by interferon.

Abstract: We report here that human leukocyte interferon preparations are capable of influencing the transition of human melanoma cells from the "A" state to the "B" phase Human melanoma cells that enter a quiescent stage at high cell density are more sensitive to the cytostatic action of interferon than those that continue to proliferate under similar conditions Cell cycle perturbations caused by interferon in these cells include a decreased transition rate out of G0-G1 ("A" state) into S ("B" phase) and a prolongation of S These findings support the idea that some metabolic event is required for progress through the G0-G1 phase of the cell cycle and is susceptible to interferon action

Recombinant DNA molecules and their use in producing human interferon-like polypeptides

Abstract: Recombinant DNA molecules and hosts transformed with them which produce polypeptides displaying a biological or immunological activity of human interferon, the gene coding for these polypeptides and methods of making and using these molecules, hosts, genes and polypeptides The recombinant DNA molecules are characterized by structural genes that code for a polypeptide displaying a biological or immulogical activity of human interferon In appropriate hosts these molecules permit the production and identification of genes and polypeptides displaying a biological or immunological activity of human interferon and their use in antiviral and antitumor or anticancer agents

Host gene influences sensitivity to interferon action selectively for influenza virus

Abstract: Several examples of genetically determined resistance to different viruses have been studied in mice1. Inborn resistance due to the allele Mx in A2G mice may be characterised as follows: resistance is specific for members of the orthomyxo family (influenza virus)2; it is expressed in different organs and cells2–6; and it is independent of a functioning immune system3,4,7. The only means of rendering resistant mice fully susceptible to influenza virus has been treatment with potent anti-interf eron serum8, indicating that interf eron is important in resistance. Interf eron is generally thought to inhibit the multiplication of all animal viruses relatively indiscriminately. Therefore, it had seemed unlikely that interferon was involved in this resistance, as A2G mice were selectively resistant to influenza virus albeit as sensitive as control mice to several other viruses4. There are, however, examples in which the genetic control of the production of interferon or the sensitivity to interferon action is expressed selectively for a given virus. Thus, De Maeyer and coworkers have shown that four different If loci control the amount of circulating interferon produced after injection of mice with Newcastle disease virus (NDV)9, mouse mammary tumour virus10, or Sendai virus (personal communication). Hanson et al.11 found that cultures of cells from C3H RV mice, resistant to Arbo B virus infection, were much more susceptible to the inhibitory effect of interferon when tested with Arbo B viruses than cultures taken from susceptible C3H mice. We present here results, showing that cultures of macrophages from mice resistant to orthomyxoviruses (Mx positive) can be protected by much smaller amounts of interferon than are necessary to protect cultures from susceptible mice when these cultures are infected with influenza virus; whereas no difference in sensitivity to interferon is observed when cultures are infected with vesicular stomatitis virus (VSV) or encephalomyocarditis virus (EMC). We believe that these results showing a genetic control of sensitivity to interferon action specific for a given virus are related to the in vivo resistance of A2G mice to influenza virus. If applicable to man, these results may also be of importance in understanding individual variations in sensitivity to viral infections.

Interferon activation of "pre-spontaneous killer" (pre-SK) cells and alteration in kinetics of lysis of both "pre-SK" and active SK cells.

Abstract: Interferon augments spontaneous killer cellular cytotoxicity (SKCC). This modulation may be vital in both tumor resistance and host viral defenses. To date, whether increased numbers of effector cells or activation of individual effector cells is responsible for this augmentation has not been established. Using a single cell assay where SK killing is directly visualized by the reading of trypan blue uptake at various time points by effector-target cell conjugates plated in agarose gel, we measured in vitro alterations in percentage of conjugate formation, number of active SK cells, and kinetics of SK cell lysis at the single cell level after 1 hr of interferon incubation. After interferon, there is no difference in number of cells that bind K-562 targets. This augmentation of cytotoxicity is due to both recruitment of new effector cells and an activation of the lytic process of both the new and already active SK cells.

Interferon induced in human leukocytes by mitogens: production, partial purification and characterization

Abstract: Interferon was induced in leukocyte suspensions from human buffy coats by exposure to phytohemagglutinin P, concanavalin A (Con A) and staphylococcal enterotoxin A, under a variety of cell culture conditions. Con A was found to rapidly (within 12 h) induce high yields of antiviral activity (1.5 units/1000 cells). Lesser yields were obtained with the other two mitogens studied. The interferon was partially purified to a spec. act. around 10(5.3) units/mg protein, by batch adsorption on controlled-pore glass (CPG) beads and desorption by ethylene glycol. This material was characterized as containing mainly gamma-type interferon. Specifically on gel filtration, a fraction of 45000 daltons was obtained which could account for virtually all antiviral activity present in the starting material. Furthermore, the ethylene glycol-eluted antiviral activity was acid-labile, serologically distinct from alpha and beta-type interferon and strictly species-specific (no activity detectable on any of the available cell species sensitive to alpha and beta-type interferon). The crude culture supernatant also contained some antiviral activity which resembled beta-type interferon in that it adsorbed to CPG, could be desorbed by pH 2 buffer, was acid-resistant and could be neutralized by a specific anti-fibroblast interferon antiserum. The CPG/ethylene glycol-purified gamma-type interefron preparation was found to inhibit the growth of certain lymphoblastoid cells (Daudi and Molt-4). It also potentiated natural killer activity of fresh donor lymphocytes. In both respects, the gamma-type interferon preparation was not significantly more active than preparations of alpha and beta-interferon of similar antiviral potency.

Epstein-Barr Virus Infection in Renal Transplant Recipients: Effects of Antithymocyte Globulin and Interferon

Abstract: We studied Epstein-Barr (EB) virus excretion and antibody in 41 renal transplant recipients enrolled in a placebo-controlled trial of human leukocyte interferon. Half the patients were also treated with antithymocyte globulin. Epstein-Barr virus excretion occurred more often in recipients of cadaver kidneys (P = 0.03) and those receiving antithymocyte globulin (P = 0.04) and less often in patients given interferon (P = 0.08). Antibody to viral capsid antigen increased fourfold or more in 12 of 22 patients treated with antithymocyte globulin and in none of the non-antithymocyte globulin-treated group (P = 0.0002). Antibody to the restricted component of early antigen rose fourfold or more in eight patients and appeared related to the occurrence of syndromes similar to those attributed to cytomegalovirus in transplant recipients. We conclude that increasing immunosuppression augments the rate of EB virus reactivation and that EB virus may be an important pathogen in heretofore ill-defined syndromes.

Common pathways of interferon and hormonal action.

Abstract: The action of interferon1 as well as polypeptide hormones2 has been shown to be transmissible between cells, possibly through gap-junctional transfer of secondary messenger molecules. This and other similarities between interferon and polypeptide hormones3 have led us to propose that there is a common cellular pathway of interferon and hormonal action. If correct, this hypothesis would predict that interferon should cause a species-specific hormonal response and a hormone should induce tissue-specific antiviral activity. If these two responses are mediated by similar secondary messengers, they should be transmissible and cross-activate cells. Here, we show that interferon caused a species-specific hormonal response (noradrenaline-like stimulation of the beat frequency of cultured mouse myocardial cells). Noradrenaline induced an interferon-like antiviral state in mouse myocardial cells but not human amnion (WISH) cells. In conditions which demonstrate interferon-induced transfer of viral resistance, exposure of co-cultures of mouse myocardial cells and WISH cells to either human interferon or noradrenaline caused an increased beat frequency in the myocardial cells and development of antiviral activity in WISH cells, respectively. These studies strongly suggest common pathways of interferon and hormonal stimulation that are transmissible between cells.

Interferon inhibits the conversion of 3T3-L1 mouse fibroblasts into adipocytes

Abstract: Confluent Swiss mouse 3T3-L1 fibroblasts slowly differentiate functionally and morphologically into adipocytes, a conversion hastened by insulin. The cells are sensitive (although less than L929 cells) to the antiviral action of mouse fibroblast interferons but not to interferons from heterologous species (human and chicken). Cultures stimulated with insulin in the presence of partially purified or electrophoretically pure mouse interferons have a much lower percentage of cells accumulating lipid than do insulin-treated control cultures. Interferon-treated cell cultures also contain much less triglyceride, cholesterol, and cholesterol esters than do replicate control cultures stimulated by insulin to differentiate. Increased de novo lipid biosynthesis that occurs during differentiation is inhibited, as determined by incorporation of [14C]acetate into lipids extractable by the Folch method. This incorporation is a sensitive bioassay of the antidifferentiation effect of interferon; less than 1 antiviral unit is inhibitory. Variously inactivated or mock interferon preparations as well as interferons from several heterologous species fail to inhibit 3T3-L1 adipocyte conversion. Interferon is inhibitory even when applied as long as 3 days after insulin stimulation. The effect of interferon does not appear to depend upon its competition with insulin for cell surface receptors. Because interferon can alter the program of events involved in conversion of 3T3-L1 fibroblasts into adipose cells, it may be able to affect the regulation of eukaryotic cell differentiation.

Prostaglandin A compounds as antiviral agents

Abstract: Prostaglandins of the A series strongly inhibit the production of Sendai virus in African green monkey kidney cells and are able to prevent the establishment of persistent infection ("carrier" state). This action is specific for prostaglandin A and is not due to alteration in the host cell metabolism or in the virus infectivity. The possibility that this effect is mediated by interferon is discussed.

Interferon as a mediator of human lymphocyte suppression.

Abstract: Evidence is presented that interferon (IF) is a major mediator of the human concanavalin A (Con A) suppressor cell. The suppressive effects of Con A-activated lymphocytes on the mitogen responses of normal responder cells were largely abrogated by addition of anti-human leukocyte IF serum. Similar suppressor activity was generated by coculture of peripheral blood leukocytes (PBL) with a melanoma cell line (MeWo) and a HeLa cell line persistently infected with measles virus that induced the production of IF by lymphocytes. A human mammary carcinoma line (MCF-7) and two bladder carcinoma lines (T24 and TCCSUP) failed to induce IF or suppression. Addition of anti-human leukocyte IF serum to suppressor cells and supernates from tumor cell-lymphocyte cocultures largely abolished suppression and neutralized the antiviral activity of such supernates. Exposure of PBL from purified protein derivative (PPD)-positive donors to PPD caused the production of suppressor activity and IF. PBL from PPD-negative donors failed to produce significant amounts of IF or to suppress on exposure to PPD. Supernates from PBL treated with virus (Newcastle disease virus [NDV]) contained IF and suppressed the mitogen responses of responder PBL. Both the suppressive and the antiviral activities of this material were eliminated after treatment with anti-IF serum. To ascertain whether antiviral and suppressive activities were mediated by the same types of IF, supernates from PBL cultured with Con A, PPD, NDV, and tumor cells were treated with anti-IF serum or acid pH. In all cases antiviral activity was neutralized in parallel with abrogation of suppressor activity. These results provide strong evidence for the role of IF as a mediator of human suppressor cell activity.

Mouse interferons: amino terminal amino acid sequences of various species

Abstract: Mouse interferons of three size classes (A, 35,000 to 40,000 daltons; B, 26,000 to 33,000 daltons; and C, 20,000 daltons) were purified from Ehrlich ascites tumor cells infected with Newcastle disease virus. The sequences of the first 24 amino acids (No. 17 has not been identified) of interferons A and B are identical. The sequence of the first 20 amino acids of interferon C differs from that of A and B in 18 positions. There is partial homology in amino terminal sequence between mouse interferons A (or B) and a human fibroblast interferon and between mouse interferon C and a human lymphoblastoid interferon.