Murine T-cell hybridomas that produce lymphokine with macrophage-activating factor activity as a constitutive product

Erickson, Kent L.; Cicurel, Lucienne; Gruys, Eilene; Fidler, Isaiah J.

doi:10.1016/0008-8749(82)90297-0

Cited by 20 publications

(6 citation statements)

References 14 publications

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“…Work is currently in progress to determine the fate of the receptor-bound ligand and whether receptor engagement is sufficient to initiate a tumoricidal response. The quantitation of this receptor-ligand interaction should also provide a means of defining the mechanisms of action of other factors that have been reported to have MAF activity but not antiviral activity (32)(33)(34).…”

Section: Receptor For Interferon-q On Macrophagesmentioning

confidence: 99%

Evidence for a gamma-interferon receptor that regulates macrophage tumoricidal activity.

Celada

Gray²,

Rinderknecht³

et al. 1984

The Journal of Experimental Medicine

430

235

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Antigen-or mitogen-stimulated T lymphocytes produce factors that can induce a number of functional and biochemical modifications in macrophage populations. These modifications include increases in endocytic, biosynthetic, secretory, and effector cell functions, as well as changes in membrane physiology and composition (1-4). This process has been called macrophage activation and the iymphokines that induce these effects are known as macrophage-activating factors (MAF).'Over the past three years, work from several laboratories has indicated that gamma-interferon (IFN-3,), the [FN produced by T lymphocytes, represents one type of MAF. Purified or partially purified preparations of IFN-5' produced by normal T cells, T cell hybridomas, or by recombinant DNA technology have been found to prime macrophages for nonspecific tumoricidal activity (5-11), induce or enhance intraceilular cytocidal reactions (12, 13), and increase expression of Ia or DR antigens on the cell surface (14-16). Using monoclonal antibodies to murine recombinant IFN-% we have recently shown that IFN-'r represents the major and possibly only lymphokine produced by concanavalin A (Con A)-stimulated normal murine splenic cells or the 24/G1 murine T cell hybridoma that can induce tumoricidal activity or Ia expression in macrophagesfl These observations have prompted an analysis of the interaction of IFN-7 with macrophage populations. It is the purpose of this report to describe this interaction on a functional and biochemical basis and to demonstrate the existence of a IFN-~, receptor on macrophages. This receptor is capable of binding either

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Section: Receptor For Interferon-q On Macrophagesmentioning

confidence: 99%

Evidence for a gamma-interferon receptor that regulates macrophage tumoricidal activity.

Celada

Gray²,

Rinderknecht³

et al. 1984

The Journal of Experimental Medicine

430

235

View full text Add to dashboard Cite

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“…Similarly, low levels of IFN-3, (0.1-1 U/ml) can significantly augment hydrogen peroxide release and induce toxoplasmacidal activity of macrophages (12). The fact that the MAF assay appears to be 5-10-fold more sensitive than the standard antiviral assay for IFN-3, may be of importance in investigations where macrophage activation is observed with no detection of antiviral activity (46). Additionally, small molecular weight factors reported to induce macrophage activation (47,48) may actually be breakdown products of IFN-3,.…”

Section: Macrophage Activation By Supernatants Of Murine T Lymphocytementioning

confidence: 99%

Biological and antigenic similarities of murine interferon-gamma and macrophage-activating factor.

Svedersky¹,

Benton²,

Berger³

et al. 1984

The Journal of Experimental Medicine

113

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The multiple biological activities present in semipurified lymphokine preparations have made it difficult to assign discrete biological functions to each lymphokine. As a result, the large number of identified lymphokine activities may actually reflect the manifestations of a few factors. While this research has also been hampered by the limited quantities of lymphokines available, hybridoma and recombinant DNA technologies have begun to help overcome these limitations.Macrophage activation has been intensively investigated because it is generally agreed that activated macrophages play an essential role in the defense against microorganisms and in the immune response against neoplasia (1). Macrophage activation mediated by macrophage activation factor (MAF) 1 and gamma interferon (IFN-'y) has been characterized by similar morphologic, metabolic, and functional changes (2-6) including stimulation of nonspecific tumoricidal activities (5), induction of Ia antigen expression (7, 8), increased Fc receptor expression (0, 10), production of plasminogen activator (I 1), and production of hydrogen peroxide (12). Several investigators (5,8,12,13) have postulated therefore that IFN-q~ and MAF may be identical. In support, Schreiber et al. (14) have recently demonstrated biosynthetic and biochemical similarities of IFN-'y and MAF produced by a murine T cell hybridoma (24/G1). Both the antiviral and MAF activities of 24/G1 cultured supernatants were neutralized by anti-IFN-% but not anti- . have demonstrated neutralization of MAF activity with polyclonal antMFN-7, definitive results could not be ascertained since these antisera were prepared from partially purified preparations and could contain antibodies that neutralize other lymphokine activities.In the present report, murine IFN-~ produced by recombinant DNA techniques (18) (>00% pure) was tested for MAF activity; special attention was given

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“…Recently, an active component in lymphokine-containing supernatants was identified as gamma-interferon (gamma-IFN) (30,31,34,38,42,47,53), and recombinant DNA-produced gamma-IFN was shown to have the same activity (26,39,40). However, lymphokines may contain compounds other than gamma-IFN that are capable of activating macrophages (17,19,31,41,44). Receptors for IFN on macrophages (13) and fibroblasts (1) have been reported, and mechanisms of activation by IFN are under investigation.…”

mentioning

confidence: 99%

Recombinant and natural gamma-interferon activation of macrophages in vitro: different dose requirements for induction of killing activity against phagocytizable and nonphagocytizable fungi

Brummer¹,

Morrison²,

Stevens³

1985

Infect Immun

122

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Recombinant murine gamma-interferon (IFN) and supernatants from concanavalin A (ConA)-stimulated spleen cells were tested for their ability to activate resident peritoneal macrophages (M+) for fungicidal activity. M4 monolayers pulsed overnight with IFN exhibited significantly enhanced fungicidal activity against Candida albicans (44 ± 12 versus 0.0%) and Blastomyces dermatitidis (34 ± 1 versus 3 ± 3%). The effect of IFN was dose dependent; however, less IFN (10 U/ml) was required to activate M4 to kill phagocytizable C. albicans than to kill nonphagocytizable B. dermatitidis (1,000 U/mI). ConA-stimulated spleen cell supernatants were also able to activate M4 for fungicidal activity against both fungi. The capacity of ConA-stimulated spleen cell supernatants to activate M4 for fungicidal activity was neutralized in the presence of antibody to murine IFN. ConA-treated monolayers acquired the ability to kill C. albicans, but not B. dermnatitidis, which was shown to be associated with residual (10%) lymphocytes in the monolayers. Lipopolysaccharide (0.001 to 10 ,ug/ml) failed to consistently activate M4 for fungicidal activity. These data show that IFN can exert an immunoregulatory role on M4 defense against these fungal pathogens.

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Murine T-cell hybridomas that produce lymphokine with macrophage-activating factor activity as a constitutive product

Cited by 20 publications

References 14 publications

Evidence for a gamma-interferon receptor that regulates macrophage tumoricidal activity.

Evidence for a gamma-interferon receptor that regulates macrophage tumoricidal activity.

Biological and antigenic similarities of murine interferon-gamma and macrophage-activating factor.

Recombinant and natural gamma-interferon activation of macrophages in vitro: different dose requirements for induction of killing activity against phagocytizable and nonphagocytizable fungi

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