Showing papers on "Interferon published in 1973"
TL;DR: It is apparent from these findings that the gene(s) for indophenol oxidase (IPO-B) and the gene for the antiviral protein are syntenic and that they are linked to human chromosome G-21.
Abstract: 13 independent mouse-human somatic cell hybrid clones derived from β-propiolactone-inactivated Sendai stimulated cell fusion of human cells with mouse cells were tested for their sensitivities to human and mouse interferon. All of them were protected by mouse interferon and only six of the clones were protected by both human and mouse interferon. Only the six that were protected by human interferon were shown to express the human dimeric form of indophenol oxidase. Complete chromosomal analysis of the clones indicated human chromosome G-21 to be the only human chromosome in common for the six clones which had both phenotypes present. Nine subclones were derived from one of the clones expressing both phenotypes. Eight of the nine subclones were shown to retain both phenotypes, whereas one subclone lost both. Chromosomal analysis of the subclones indicated the loss of chromosome G-21 from the subclone which lost both phenotypes. It is apparent from these findings that the gene(s) for indophenol oxidase (IPO-B) and the gene(s) for the antiviral protein are syntenic and that they are linked to human chromosome G-21.
277 citations
Journal Article•
TL;DR: Evidence is presented which emphasizes the striking similarities in properties of MIF and Type II interferon, although it is not possible to determine whether the two mediators are the same or different protein molecules.
Abstract: Further evidence is presented of the coordinate production and similar properties of two mediators, migration inhibitory factor (MIF) and interferon, in the circulation of BCG-infected mice inoculated with specific antigen (Old Tuberculin, OT). In addition, the interferon elicited by OT in BCG-infected mice is shown to be a distinct molecular species of viral inhibitor and is designated “Type II interferon.” The designation “Type I interferon” is used to describe the viral inhibitor produced in BCG-infected or control mice given nonspecific stimuli such as bacterial lipopolysaccharide (LPS) or Newcastle disease virus (NDV). Although Type II interferon possesses the biologic attributes required to classify a viral inhibitor as “interferon,” it, as well as MIF, differs markedly from Type I interferon in stability at pH 2 and at 56°C, range of species specificity, and antigenicity. Antibodies against highly purified L cell interferon induced by NDV (anti-Type I interferon antibodies) neutralize the activity of interferons elicited in mice by nonspecific stimuli such as LPS or NDV. In contrast, the antiviral activity of Type II interferon and the macrophage-inhibitory activity of MIF, elicited by specific antigen in mice with delayed hypersensitivity, are not affected by high concentrations of antibody against Type I interferon. Evidence is presented which emphasizes the striking similarities in properties of MIF and Type II interferon, although it is not possible to determine whether the two mediators are the same or different protein molecules.
273 citations
TL;DR: In volunteers, a single day of prophylaxis with intranasal interferon only slightly delayed the onset of an influenza-B infection, and did not prevent the illness or reduce its severity, but by using a greater daily dosage of interferOn, a statistically significant prevention of clinical symptoms and virus-shedding was achieved after challenge of volunteers with rhinovirus 4.
241 citations
TL;DR: It is concluded that interferon treatment of L 1210 cells is accompanied by modifications of the cell surface, as determined by their alloantibody- absorbing capacity.
Abstract: Preparations of mouse interferon enhanced the expression of surface antigens of murine leukemia L 1210 cells, as determined by their alloantibody-absorbing capacity. The factor responsible for the enhancement of surface antigen expression could not be dissociated from the antiviral activity of interferon by standard physicochemical means. Likewise, interferon did not increase the antibody-absorbing capacity of an interferon-resistant subline of L 1210 cells. We conclude that interferon treatment of L 1210 cells is accompanied by modifications of the cell surface.
198 citations
TL;DR: Although hypersensitive to specific antigen by footpad swelling tests, mice sensitized with complete Freund adjuvant failed to produce MIF or interferon when they were inoculated intravenously with OT or living BCG cells.
Abstract: When mice infected with Mycobacterium tuberculosis strain BCG were inoculated intravenously with old tuberculin (OT) or living BCG cells, both migration inhibitory factor (MIF) and interferon appeared in the circulation within a few hours. In such animals, which showed delayed hypersensitivity by footpad tests, as little as 1.5 mg of OT or as few as 1.7 x 10(6) bacteria per mouse were capable of eliciting circulating MIF and interferon. Uninfected animals inoculated with large doses of OT or living BCG cells did not produce MIF or interferon. When nonspecific stimuli such as bacterial lipopolysaccharide (LPS; from Salmonella typhimurium strain LT-2), heat-killed Brucella abortus, Newcastle disease virus (NDV), and polyinosinic acid:polycytidilic acid (poly I:C) were inoculated intravenously into BCG-infected mice, MIF was produced in the circulation of animals challenged with LPS or Brucella but not in those challenged with NDV or poly I:C, although all the stimuli were capable of eliciting an interferon response. The interferon elicited in BCG-infected mice by specific antigen differed in at least one important property from the viral inhibitor produced by the nonspecific stimuli. The interferon which appeared after injection of OT or living BCG cells was destroyed by treatment at pH 2 for 24 hr at 4C, whereas the interferons produced after injection of the nonspecific stimuli were stable under the same conditions. The MIF activity in plasma from sensitized mice inoculated with specific antigen was also destroyed by treatment at pH 2. When mouse plasma containing both MIF and interferon activity was filtered through Sephadex G-100, both mediators were excluded in the same peak fractions. Sensitization of mice with complete Freund adjuvant instead of infection with BCG cells produces a different pattern of response. Although hypersensitive to specific antigen by footpad swelling tests, mice sensitized with complete Freund adjuvant failed to produce MIF or interferon when they were inoculated intravenously with OT or living BCG cells.
157 citations
TL;DR: It is suggested that both antibody and leukocytes are needed to cure HSV infections.
Abstract: Antibody to herpes simplex virus (HSV) plus complement destroyed HSV-infected cells but did not stop the spread of the infection. Studies on the relationship between the time of appearance of viral antigens on the cell surface, immunological destruction of the cells by antiviral antibody and complement, and transfer of the virus to adjacent cells showed that the virus spread from infected to uninfected cells before the infected cells were susceptible to immunological destruction. Incubation of infected monolayers with leukocytes, however, stopped the spread of the virus by nonspecifically damaging both infected and uninfected cells and by presumably breaking intercellular bridges. When leukocytes were removed from infected monolayers, viral plaques developed. If, however, antiviral antibody and complement were added to monolayers before the leukocytes were removed, the development of plaques was prevented. These findings suggest that both antibody and leukocytes are needed to cure HSV infections.
134 citations
TL;DR: Defective interfering T particles of vesicular stomatitis virus provide remarkable protection against viral disease and death when introduced intracerebrally in large numbers along with an otherwise rapidly fatal low dose of standard infectious virus.
Abstract: Defective interfering T particles of vesicular stomatitis virus provide remarkable protection against viral disease and death when introduced intracerebrally in large numbers along with an otherwise rapidly fatal low dose of standard infectious virus. This profound prophylactic effect of defective T particles is due to homologous autointerference since it is serotype-specific and interferon is not induced. This protective effect can be demonstrated only with preparations of T particles that have been purified completely free of infectious virions. When pure T particles are injected intracerebrally along with large doses of infectious virus, they convert an otherwise rapidly fatal disease process to a slowly progressing virus infection that generally terminates in death after many days of wasting disease and paralysis. Intracerebral injection of virus-free T particles alone is apparently innocuous to mice and stimulates immunity to massive doses of homologous infectious virus.
In vitro, virus-free T particles at extremely high multiplicities depress cellular RNA and protein synthesis and kill BHK21 cells in culture, but do not exhibit such effects at moderately high multiplicities.
124 citations
TL;DR: Transcription of interferon messenger RNA was apparently not affected wheninterferon synthesis was suppressed to various degrees by different inhibitors of protein synthesis, indicating the independence of transcription and translation.
Abstract: Interferon production was induced in a strain of human diploid foreskin cells with poly(I)·poly(C). Cycloheximide was included in the culture medium at the time of addition of the inducer. Actinomycin D was added to the cultures 4 or 5 hr later, before the inhibition of protein synthesis was reversed at 6 hr. Thus, subsequent interferon synthesis had to be directed by messenger RNA synthesized before addition of actinomycin D. The amount of interferon produced after such treatment was about 50-fold greater than in cells induced with poly(I)·poly(C) but not treated with inhibitors. Experiments using cordycepin suggested that in spite of the continued presence of the inducer the synthesis of the bulk of interferon messenger RNA was completed within the first 2 hr of exposure of cells to poly(I)·poly(C) and cycloheximide. Transcription of interferon messenger RNA was apparently not affected when interferon synthesis was suppressed to various degrees by different inhibitors of protein synthesis, indicating the independence of transcription and translation. The high rate of interferon synthesis after the reversal of cycloheximide action was more sustained at 32° than at 37°. The rate of decrease of overall protein synthesis in cells treated with actinomycin D and then incubated either at 32° or 37° showed a similar dependence on incubation temperature, suggesting that the stability of messenger RNA (or of another actinomycin D-sensitive component required for protein synthesis) was greater at the lower temperature.
112 citations
111 citations
Journal Article•
TL;DR: Mouse interferon produced in L cells was subjected to affinity chromatography on Sepharose-bound anti-interferon globulin and adsorbed to remove antibodies against proteins derived from normal L cells, medium, and inducer virus preparation to permitted selective elimination of identified contaminant antigens.
Abstract: Mouse interferon produced in L cells was subjected to affinity chromatography on Sepharose-bound anti-interferon globulin. The hyperimmune anti-interferon serum was specifically adsorbed to remove antibodies against proteins derived from normal L cells, medium, and inducer virus preparation. The method permitted selective elimination of identified contaminant antigens from crude interferon preparations. Recovery of interferon was quantitative, and purification during this step was from 20- to 50-fold. Specific activities in peak fractions ranged from 1 to 2.7 × 108 National Institutes of Health reference units per mg protein. Interferons induced by irradiated Newcastle disease virus and poly I:C were purified to the same degree.
108 citations
TL;DR: It is established that interferon induces a block in genetic translation in noninfected L cells.
Abstract: When noninfected L-cell suspension cultures are treated with interferon (specific activities superior to 106 reference units per mg of protein), the cell-free cytoplasmic extracts obtained are inactive for the translation of exogenous natural mRNAs. The dose-response curve shows that comparable amounts of interferon are required to produce a 50% reduction of Mengo virus multiplication in vivo and Mengo RNA translation in vitro. With higher doses of interferon, Mengo RNA translation is completely abolished, while poly U translation and endogenous protein synthesis are only slightly affected. The inactivation of Mengo RNA translation is reversible; after removal of interferon, normal translation activity is regained together with the ability to support Mengo virus multiplication. Fractionation of the cell-free extracts shows that the effect is localized in the fraction which can be washed off the ribosomes by high salt. These results establish that interferon induces a block in genetic translation in noninfected L cells.
TL;DR: A carrier state of Sindbis virus with cycling pattern was induced in the mouse L cells and in the established mouse embryo cell line MEC/c, and highly specific rabbit anti-interferon globulin incorporated into the growth medium of carrier L line caused a 100- to 1000-fold stimulation of the synthesis.
Abstract: Summary
A carrier state of Sindbis virus with cycling pattern was induced in the mouse L cells and in the established mouse embryo cell line MEC/c. Chick-adapted virus readily induced the persistent infection whereas the mouse-adapted virus killed cultures during the first passage. In the MEC/c line small (sp) and large (lp) plaque mutants of Sindbis virus produced more stable carrier state than the giant (gp) plaque mutant. The persistently infected cultures periodically produced small amounts of interferon. Highly specific rabbit anti-interferon globulin, which can neutralize mouse interferon, incorporated into the growth medium of carrier L line caused a 100- to 1000-fold stimulation of the synthesis of Sindbis virus after incubation for 5 days at 37 °C. The activated virus destroyed the carrier culture.
TL;DR: Human leucocyte interferon was rapidly cleared from the circulation of rabbits receiving 3 million units intravenously, but the clearance rate was greatly decreased after 1 h, and no interferons were detected in the serum after oral administration of 6 million units of human Interferon.
Abstract: Summary
Human leucocyte interferon was rapidly cleared from the circulation of rabbits receiving 3 million units intravenously, but the clearance rate was greatly decreased after 1 h. The early half-time was 13 min and the late half-time 73 min. No circulating interferon was detected beyond 6 h. Repeated injections did not affect the clearance rate.
Intramuscular injection of 3 million units of human or rabbit interferon maintained a relatively stable interferon level in the serum for 12 h. Higher doses raised the level and prolonged the persistence of circulating interferon. A single intramuscular injection of 30 million units of human interferon maintained a detectable interferon level in the serum for 48 h. Subcutaneous injections resulted in even longer persistence of measurable interferon in the blood.
No interferon was detected in the serum after oral administration of 6 million units of human interferon.
TL;DR: Polyribocytidylic acid, endotoxin, polycarboxylate plastics or polysaccharides, and other polyanions induce interferon production and enhance antibody production, cell-mediated immunity, and reticuloendothelial activity.
Abstract: POLYRIBOINOSINIC acid: polyribocytidylic acid [poly (rI)·poly (rC)], endotoxin, polycarboxylate plastics or polysaccharides, and other polyanions induce interferon production (see reviews ref. 1 and 2). They also enhance antibody production3,4, cell-mediated immunity5, and reticuloendothelial activity4,6. It is not yet clear whether or not any of these latter effects are mediated through the action of interferon.
TL;DR: The production of interferon by human diploid cells stimulated by poly-I:C can be increased by pretreatment of the cells with interferons by combining priming with a superinduction schedule adapted from that described for rabbit kidney cultures.
Abstract: Summary
The production of interferon by human diploid cells stimulated by poly-I:C can be increased by pretreatment of the cells with interferon (priming effect). Large amounts of interferon (30000 units/ml) can be obtained by combining priming with a superinduction schedule adapted from that described for rabbit kidney cultures (Tan et al. 1970; Vilcek & Ng, 1971). Human plasma protein could replace bovine serum albumin in the production medium.
TL;DR: The dose-response curve shows that in the authors' conditions the translation of cellular messengers is as sensitive to impairment by the inhibitor(s) as that of viral messengers (from reovirus or from encephalomyocarditis virus).
TL;DR: Annealing tests showed that unlabeled WSN RNA could successfully compete with at least 75% of the 32 P-labeled nucleic acid fraction extracted from infected cells and no transcription could be demonstrated by the method employed in infected cells treated with either actinomycin D or interferon.
TL;DR: It was concluded that interferon induction elicited by the lytic reovirus multiplication cycle is triggered by some event which depends on the formation of progeny virus particles.
TL;DR: It is likely that the interferon molecule acts on the cell receptor without being detached from the beads, however, the data do not exclude the possibility of a small loss ofinterferon, or fragments of it, after contact with the cell.
Abstract: Interferon, covalently bound to Sepharose 4B activated by cyanogen bromide, induces the antiviral state in sensitive cells. The antiviral effect is neutralized by antiserum specific to interferon and is recovered thereafter when the antibody is detached from the interferon by treatment at low pH. Binding interferon to Sepharose increases the stability of the molecule. It is likely that the interferon molecule acts on the cell receptor without being detached from the beads. However, the data do not exclude the possibility of a small loss of interferon, or fragments of it, after contact with the cell.
TL;DR: At least a two-cell requirement for the production of interferon in response to PHA, Con A or PPD stimulation is suggested and it is suggested that the interferons-producing cells do not belong to the thymus-dependent lymphocyte subpopulation.
TL;DR: The results are interpreted as indicating that non‐infectious A‐type particles are synthetized by a mechanism different from that by which infectious C‐ type particles are generated.
Abstract: Three types of oncornavirus-carrying mouse cell lines were studied. Replication of endogenous sarcoma or leukemia viruses in cell lines producing the infectious viruses was as sensitive to inter feron as that of exogenous vesicular stomatitis virus (VSV). Replication of non-infectious C-type virus in S+L− cells which carry a rescuable Moloney sarcoma virus (MSV) genome did not respond to interferon. However, this cell line was also found to be 70 times less responsive to interferon when tested by an exogenous VSV challenge. Finally, after exposure to interferon, M04 cells, which carry a rescuable MSV genome and produce non-infectious A-type particles, developed normal resistance to VSV. Yet, high doses of interferon could not prevent the induction of surplus A-type particles by bromodeoxyuridine (BDU) and dimethylsulfoxide (DMSO). The results are interpreted as indicating that non-infectious A-type particles are synthetized by a mechanism different from that by which infectious C-type particles are generated.
TL;DR: Parenteral injection of this compound protected mice against lethal infections with encephalomyocarditis and Semliki Forest viruses and effectively suppressed pox formation by vaccinia infection.
Abstract: CP-20,961, N,N-dioctadecyl-N′, N′-bis(2-hydroxyethyl)propanediamine, is an antiviral drug with low acute toxicity in mice. Parenteral injection of this compound protected mice against lethal infections with encephalomyocarditis and Semliki Forest viruses and effectively suppressed pox formation by vaccinia infection. Maximal antiviral effects were observed when CP-20,961 was administered 6 to 12 h before infection. An interferon detected in plasma 12 to 20 h after the drug was given appeared to mediate these effects. Comparison of the minimal effective and lethal doses in mice established a therapeutic index of 300.
TL;DR: No obvious association between increased survival and the levels of antibody and interferon in serum of the challenged animals, but these serum factors still must be considered as possible mediators of the protection conferred by sensitized spleen cells.
Abstract: The role of cell-mediated protection against infection with herpes simplex virus was studied by adoptive immunity. Sensitized spleen cells, obtained from syngeneic mice immunized with herpes simplex virus, protected recipient mice against lethal challenge with herpes simplex virus. Survival was significantly greater in challenged mice that had received washed spleen cells from donor animals immunized with herpes simplex than from control donors. This increase in survival after challenge was associated with a significant decrease in titers of virus in the brains of mice that had received specifically sensitized cells. The decrease in viral titers was evident during the period after challenge when titers of virus peak and most deaths occur. There was no obvious association between increased survival and the levels of antibody and interferon in serum of the challenged animals, but these serum factors still must be considered as possible mediators of the protection conferred by sensitized spleen cells.
TL;DR: It appeared that the low levels of interferon induced in the nasopharynx by the ts virus in vivo were a consequence of the low level of virus multiplication at that site.
Abstract: volunteers. The amount of interferon in the NP washes of these volunteers was 15-fold less than that induced by wild-type virus. In addition, interferon was detected for a shorter period in men infected with the ts-1[E] virus. There was a strong correlation between the level of virus multiplication and the amount of interferon induced in the NP washes by either the ts or wild-type virus. In vitro, the ts and wild-type viruses had similar sensitivities to interferon; in addition, under conditions that were permissive for the ts virus (34 C), it stimulated as much interferon and interference in tissue culture as wild-type virus. It appeared that the low levels of interferon induced in the nasopharynx by the ts virus in vivo were a consequence of the low level of virus multiplication at that site. Furthermore, the mechanism(s) responsible for the attenuation of this ts virus does not seem to be related to an increased production of interferon in the nasopharynx or to an enhanced sensitivity of this virus to interferon.
TL;DR: The effect of interferon andinterferon inducers on the proliferation of allogeneic spleen cells or syngeneic bone marrow cells injected into heavily-irradiated mice is investigated.
Abstract: Interferon preparations exhibit a marked antitumour effect in mice inoculated with allogeneic or syngeneic transplantable tumours1–4. The question arises whether this inhibitory effect is restricted to neoplastic cells or whether interferon also inhibits the multiplication of normal cells in vivo. Although it inhibited the division of normal mouse cells in vitro (refs. 5–7 and M. Ohwaki, Y. Kawade and E. Knight, personal communication), daily inoculation of concentrated interferon preparations did not affect the growth or development of newborn mice8. We have investigated the effect of interferon and interferon inducers on the proliferation of allogeneic spleen cells or syngeneic bone marrow cells injected into heavily-irradiated mice.
TL;DR: The results of the experiments presented here support the hypothesis and suggest the possibility that both CSF and interferon may be mutually antagonistic regulators of cell division.
Abstract: INTERFERON preparations have been shown to inhibit the multiplication of tumour cells in vitro1–4 and more recently comparable preparations have also been shown to inhibit normal cell division. Thus, inhibition has been observed in %of mouse embryo fibroblasts5, of weanling mouse kidney5, of stimulated mouse lymphocytes6 and of the formation of granulocyte/macrophage colonies derived from mouse and rabbit bone marrow7–9. In the course of investigating the effect of mouse and rabbit interferons from different sources on bone marrow colony formation in agar, it became apparent that a strict correlation did not always exist between the antiviral titre and the colony inhibiting titre of interferon preparations derived from cell culture interferon, whereas it did exist when interferon preparations derived from mouse serum or brain were used. The development of granulocyte/macrophage colonies in agar is dependent upon the presence and concentration of colony stimulating factor (CSF)10, so the most likely explanation for the lack of correlation observed in testing some interferon preparations was the presence of significant amounts of CSF in these preparations. The results of the experiments presented here support this hypothesis and suggest the possibility that both CSF and interferon may be mutually antagonistic regulators of cell division.
TL;DR: It was found that all three narcotic analgesics significantly reduced the level of serum interferon induced by either poly I:C or endotoxin, and levels of certain tissues particularly spleen were also depressed in morphine–treated animals.
Abstract: SummaryMorphine, Dilaudid, and methadone were injected into mice in order to assess their effect on interferon production. It was found that all three narcotic analgesics significantly reduced the level of serum interferon induced by either poly I:C or endotoxin. The level of inhibition was directly related to drug dosage. The inhibitory effect of morphine can persist at least 9 days following a single injection. Interferon levels of certain tissues particularly spleen were also depressed in morphine–treated animals. This effect on the level of interferon does not appear to be mediated through an effect on body temperature nor can it be eliminated by the morphine antagonist naloxone. These drugs were also tested on cells in vitro using poly I:C as an inducer and do not appear to have a major effect on either the induction or the action of interferon in vitro.The authors thank Dr. John J. Dallman, Department of Community Medicine, Medical College of Georgia for his assistance in the statistical treatment o...
Patent•
30 Oct 1973TL;DR: In this paper, the polyriboinosinate and polycytidylate complex (rI n.rC n ) are modified to yield unpaired bases (uracil or guanine) along the polyytidymate strand which render the complexes more readily hydrolyzable by nucleases present in living cells.
Abstract: The present invention relates to the induction of interferon production in the cells of living organisms, including human beings. According to the invention, nucleic acid complexes, such as the polyriboinosinate and polycytidylate complex (rI n .rC n ), are modified to yield unpaired bases (uracil or guanine) along the polycytidylate strand which render the complexes more readily hydrolyzable by nucleases present in living cells. The modified complexes retain their ability to stimulate interferon release by the cells but are rendered more vulnerable to destruction within the cells, the modified complexes being significantly less toxic than the original complexes. In addition, polyinosinate strand now has been prepared to contain 5-16% 2'-O-methyl inosinate residues, designated as (rI 5-20 ,2'-MeI) n . The new complex (rI 5-20 ,2'-MeI) n .rC n , exhibits 100-fold more activity than rI n .rC n as an interferon inducer in human cells.
TL;DR: There is a marked inhibition by interferon of liver regeneration after partial hepatectomy in mice inoculated with allogeneic or syngeneic transplantahle tumours.
Abstract: INTERFERON exhibits a marked antitumour effect in mice inoculated with allogeneic or syngeneic transplantahle tumours1–3, but comparable interferon preparations did not affect the growth or development of newborn mice4. It is important from both a theoretical and a practical point of view to determine whether interferon can inhibit normal cell division in the animal. It has been shown that interferon preparations inhibited the multiplication of normal adult allogeneic spleen cells and syngeneic bone marrow cells injected into heavily X-irradiated mice5. Jahiel and his co-workers demonstrated that three interferon inducers, Newcastle disease virus (NDV), polyinosinicpolycytidylic acid and statolon, inhibited the mitbtic response of liver cells after partial hepatectomy6, but that administration of interferon itself did not inhibit this response7. Now that potent and relatively purified mouse interferon preparations are available, we have used this experimental system, and report here a marked inhibition by interferon of liver regeneration after partial hepatectomy.
TL;DR: Experiments show that the amount of CS factor produced by unstimulated cultures of spleen, thymus and bone marrow cells spontaneously produce CS factor increases when certain %are stimulated by allogeneic cells, soluble antigen (PPD) or phyto-haemagglutinin (PHA).
Abstract: INTERFERON inhibits the development of granulocyte/macrophage colonies in vitro1–3. Colony stimulating (CS) factor, necessary for in vitro growth of colonies from their progenitor cells and interferon seem to have antagonistic effects in this system (ref. 3 and preceding letter19). As interferon is released during the later stages of some immunological reactions in vitro4 and inhibits DNA synthesis in such cultures5 I studied the possibility that CS factor could be involved in these reactions. Unstimulated cultures of spleen, thymus and bone marrow cells spontaneously produce CS factor, but our experiments show that the amount increases when certain %are stimulated by allogeneic cells, soluble antigen (PPD) or phyto-haemagglutinin (PHA).