Production and Properties of Immune Interferon from Spleen Cell Cultures of <i>Toxoplasma</i>‐Infected Mice

Shirahata, Toshikazu; Shimizu, Kiheiji

doi:10.1111/j.1348-0421.1980.tb02915.x

Cited by 36 publications

(30 citation statements)

References 28 publications

(32 reference statements)

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“…One report described the inhibition of the growth of Toxoplasma and Besnoitia in hamster fibroblasts and kidney cells treated with supernatants derived from cultures of antigen-stimulated hamster lymphocytes (31). Inhibition of the growth of Toxoplasma in mouse L929 cells treated with supernatants obtained from cultures of antigen-stimulated mouse spleen cells has also been noted (32). The anti-Toxoplasma factor in this system had certain properties in common with interferon-y (32).…”

Section: Discussionmentioning

confidence: 86%

Inhibition of the growth of Rickettsia prowazekii in cultured fibroblasts by lymphokines.

Turco¹,

Winkler²

1983

The Journal of Experimental Medicine

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The effect of lymphokine treatment of mouse and human fibroblast cell lines on the growth of Rickettsia prowazekii within the fibroblasts was studied. Treatment of mouse L929 cells with concanavalin A- or antigen-induced mouse lymphokines both before and after infection with R. prowazekii led to clearance of the rickettsiae from a substantial proportion of the cells and suppression of rickettsial growth in those cells which remained infected. Similar but less dramatic anti-rickettsial effects were observed in L929 cells treated with mouse lymphokines either only before or after infection with rickettsiae. Mouse lymphokine treatment of L929 cells had similar anti-rickettsial effects on the avirulent E strain and the virulent Breinl strain of R. prowazekii. Addition of cycloheximide or emetine to L929 cells at the same time as the lymphokines markedly suppressed the inhibition of rickettsial growth by the lymphokines. Mouse lymphokine treatment inhibited rickettsial survival and growth in mouse 3T3-A31 cells as well as in mouse L929 cells, but had no effect on rickettsial survival and growth in human foreskin fibroblasts. Conversely, concanavalin A-induced human lymphokines inhibited rickettsial survival and growth in human foreskin fibroblasts but had no effect on rickettsial survival and growth in mouse L929 cells. The rickettsia inhibitory activity in concanavalin A-induced mouse lymphokines was destroyed by heating the lymphokines at 80 degrees C for 10 min or by holding the lymphokines at pH 2 for 24 h but was retained after heating at 56 degrees C for 30 min.

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Section: Discussionmentioning

confidence: 86%

Inhibition of the growth of Rickettsia prowazekii in cultured fibroblasts by lymphokines.

Turco¹,

Winkler²

1983

The Journal of Experimental Medicine

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“…In addition, in a number of previous studies, various IFN preparations have also been reported to enhance the antimicrobial activity of different cell populations against other nonviral intracellular pathogens, including T. gondii (12)(13)(14)(15), Rickettsia akari (16), and Mycobacterium tuberculosis (17). In separate studies using the same monoclonal anti-IFN-y antibody and additional lymphokines and other IFN-y preparations (including pure, recombinant IFN-'y), we have also recently observed that the capacity of human monocyte-derived macrophages to respond to lymphokine with (a) enhanced oxidative burst activity and oxygen-dependent killing of T. gondii (18), and (b) oxygen-independent inhibition of in-tracellular Chlamydia psittaci and T. gondii replication (5,19) are both dependent upon and can be induced by IFN-y.…”

Section: Discussionmentioning

confidence: 99%

Killing of intracellular Leishmania donovani by lymphokine-stimulated human mononuclear phagocytes. Evidence that interferon-gamma is the activating lymphokine.

Murray¹,

Rubin²,

Rothermel³

1983

J. Clin. Invest.

380

188

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A B ST R A C T We have found that the crude lymphokines, which prime the human monocyte-derived macrophage to generate H202 and exert microbicidal activity against intracellular Leishmania donovani, are rich in interferon (IFN)-y (600-3,000 U/ml). To determine the role of this specific lymphocyte product in macrophage activation, lymphokines were pretreated with a monoclonal antibody that neutralizes human IFN-y. Antibody exposure completely abolished the capacity of both mitogen-and antigen-stimulated lymphokines to either enhance macrophage H202 release or induce leishmanicidal activity. In addition, partially purified and pure recombinant human IFN-'y were as effective as crude lymphokines in activating macrophages, and 3 d of treatment with 300 U/ml resulted in a seven-to eightfold increase in H202 generation and the intracellular killing of both L. donovani promastigotes and amastigotes. The ability of crude lymphokines to induce monocytes and macrophages from a patient with chronic granulomatous disease to kill L. donovani promastigotes was similarly abrogated by anti-IFN-'y antibody, and could also be achieved by IFN-'y alone. These results suggest that IFN-y is the key macrophage-activating molecule present within human lymphokines, and indicate that

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“…Several laboratories have reported that interferon blocked the growth of T. gondii in cultured fibroblast or epithelial cells (4)(5)(6). Shirahata and Shimizu (6) have presented evidence that IFN-y is the active substance in their studies of the inhibition of T. gondii. Experiments done in this laboratory showed that human recombinant IFN-a and IFN-,B had no effect on T. gondii.…”

mentioning

confidence: 99%

Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan.

Pfefferkorn¹

1984

Proc. Natl. Acad. Sci. U.S.A.

777

576

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Treatment of human fibroblasts with human recombinant y interferon blocked the growth of Toxoplasma gondii, an obligate intracellular protozoan parasite. Growth Interferons are currently assigned to three classes on the basis of the cells that produce them (reviewed in ref. 1); a and X interferons (IFN-a and IFN-f) are produced by leukocytes and fibroblasts, respectively, in response to viral infection, whereas y interferon (IFN-y) is produced by T-lymphocytes when stimulated by mitogens or by antigens to which they had previously been sensitized. Each of these interferons was originally identified through its inhibition of viral growth. In addition to their well-documented antiviral activities, crude interferons also occasionally have been observed to suppress the growth of other nonviral intracellular infectious agents (reviewed in ref.2). In studying the antiviral-like action of interferon against Toxoplasma gondii, an obligate intracellular protozoan parasite, it is important that macrophages not be used as the host cells. Activated macrophages are known to kill intracellular T. gondii (3), and macrophageactivating factor might be present in crude interferon preparations. Indeed, macrophage-activating factor and IFN-y may well be the same substance. Several laboratories have reported that interferon blocked the growth of T. gondii in cultured fibroblast or epithelial cells (4-6). Shirahata and Shimizu (6) have presented evidence that IFN-y is the active substance in their studies of the inhibition of T. gondii. Experiments done in this laboratory showed that human recombinant IFN-a and IFN-,B had no effect on T. gondii. However, treatment of human fibroblasts with 8 to 16 units of human recombinant IFN-y per ml blocked the growth of T. gondii. This IFN-y inhibited vesicular stomatitis virus at 4 units/ml with the same line of human fibroblast as host cells (unpublished data).The biochemical basis of the antiviral state induced by the various interferons is now reasonably well understood (reviewed in ref. 7). In reviewing the action of interferon on nonviral agents, Vildek and Jahiel (2) suggested 13 yr ago that inhibitory mechanisms different from those that block viral growth were likely to be involved. This report presents evidence for an antitoxoplasma mechanism induced by IFNy that is totally different from the well-studied antiviral state induced by interferons. MATERIALS AND METHODSHost Cells and Parasites. Human fibroblasts were grown in Eagle's (8) minimal essential medium supplemented with antibiotics and 10% fetal bovine serum. The serum concentration was reduced to 3% for infection or for treatment with interferon. Medium without tryptophan was prepared from a kit supplied by GIBCO and supplemented with dialyzed fetal bovine serum. Cloned T. gondii of the RH strain were maintained by serial passage in human fibroblast cultures and assayed by plaque formation, with the results reported as plaque-forming units as described (9).Interferons and Their Titration. Human recombinant IFNa, IFN-p,...

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Production and Properties of Immune Interferon from Spleen Cell Cultures of Toxoplasma‐Infected Mice

Cited by 36 publications

References 28 publications

Inhibition of the growth of Rickettsia prowazekii in cultured fibroblasts by lymphokines.

Inhibition of the growth of Rickettsia prowazekii in cultured fibroblasts by lymphokines.

Killing of intracellular Leishmania donovani by lymphokine-stimulated human mononuclear phagocytes. Evidence that interferon-gamma is the activating lymphokine.

Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan.

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