Interferon inhibition of the primary in vitro antibody response to a thymus-independent antigen

Johnson, Howard M.; Bukovic, Joann A.; Baron, Samuel

doi:10.1016/0008-8749(75)90089-1

Cited by 45 publications

(34 citation statements)

References 17 publications

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“…It appears from the above that ACTH and IFN have several common immunosuppressive properties. These include blockage by 2-mercaptoethanol (10), similar kinetics of action (11), preferential suppression of T-cell-dependent antibody responses over T-cell-independent responses (12), and suppression of critical early events in the antibody response (11,13). It is quite conceivable that the lymphocyte-derived ACTH, acting separately or coordinately with the IFN, mediated some of the biological effects attributable to IFN, such as regulation of the immune response.…”

Section: Resultsmentioning

confidence: 99%

Regulation of the in vitro antibody response by neuroendocrine hormones

Johnson

Smith

Torres

et al. 1982

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

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338

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Treatment of lymphocytes with inducers of interferon a (IFN-a) results in the production of corticotropin (ACTH) and endorphin-like activities. The pro-opiomelanocortinderived hormones ACTH and a-, (-, and y-endorphin and the structurally related hormones [Leu]-and [Metlenkephalin were therefore tested for their effects on the in vitro antibody response ofmouse spleen cells. ACTH and a-endorphin were potent inhibitors (.80% suppression) of the antibody response to the T-celldependent antigen sheep erythrocytes at a concentration of 0.5 p.M.[Met]-and [Leu]enkephalin were moderate inhibitors (approximately 60% suppression) at 0.2-2 FM, and (-and y-endorphin were minimal inhibitors (approximately 20% suppression) at 5-6 pAM. At higher concentrations ACTH also inhibited the antibody response to the T-cell-independent antigen dinitrophenylFicoll, suggesting that T-cell function was more sensitive to blockage by these hormones than was B-cell function. ACTH and IFN had similar suppression properties; thus, the hormone-like activities associated with IFN-a may play a role in IFN-induced immunosuppression. a-Endorphin immunosuppression was blocked by naloxone, which suggested that a-endorphin exerted its effects through binding to opiate-like receptors on the spleen cells. The failure of (3-endorphin to suppress the immune response significandy was not due to its failure to bind to the opiate-like receptors because it blocked a-endorphin-induced suppression. Direct evidence for both opiate and ACTH receptors on the spleen cells was obtained in binding studies with labeled enkephalin and ACTH. Such studies revealed the presence of both high-and low-affminty receptors. The data show that neuroendocrine polypeptide hormones can regulate the immune response.It has been shown recently that interferons (IFNs) have hormonal or hormone-like activities and share common pathways of cell activation with polypeptide hormones (1-3). Additionally, based on biological, biochemical, and antigenic characterization, we have shown that human lymphocytes stimulated with IFN-a inducers produce corticotropin (ACTH) and endorphin-like substances (4-6). The findings support a regulatory circuit between the immune and neuroendocrine systems which operates by known hormones that are common to both systems. RESULTS AND DISCUSSIONACTH suppressed the C57BL/6 mouse spleen cell PFC response to both SRBC (T-cell-dependent antigen) and DNP-Ficoll (T-cell-independent antigen) as shown in the dose-response curves (Fig. 1). The slopes for ACTH suppression of the antibody response to the two antigens were essentially the same, but the anti-SRBC response was more sensitive to suppression. Approximately 80% of the anti-SRBC PFC response was suppressed with 0.5 AM ACTH, whereas 2 A.M was required for comparable suppression of the anti-DNP-Ficoll response. Treatment of spleen cells with anti-Thy 1.2 antibody in order to remove T cells did not alter ACTH suppression of the anti-DNP-Ficoll PFC response (data not shown). Thus, ACTH suppressed the antibo...

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Section: Resultsmentioning

confidence: 99%

Regulation of the in vitro antibody response by neuroendocrine hormones

Johnson

Smith

Torres

et al. 1982

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

Self Cite

338

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“…Antimitotic agents can exert their inhibitory effect at different steps of the cell cycle [13]. Some in hibitors like interferon inhibit the Go-G| transition, but most of the inhibitors arrest the cycle in G i by raising cAMP [14,15], To explore the hypothesis of an inhibition of the mitotic cycle by SDIF, the effect of SDIF on the production and action of 1L-2 was in vestigated. IL-2 is produced by lymphocytes once ac tivated by a mitogen or an antigen, which are required to induce the transition from Go to G| [16].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Cytotoxic T Lymphocytes by a Schistosome-Derived Inhibitory Factor Is Independent of an Inhibition of the Production of Interleukin 2

Mazingue¹,

Dessaint²,

Schmitt-Verhulst³

et al. 1983

Int Arch Allergy Immunol

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Schistosome-derived inhibitory factor (SDIF) was shown to inhibit lymphocyte proliferation. While SDIF is not toxic to lymphoid cells, the generation of cytotoxic effector cells was inhibited by SDIF in a mixed lymphocyte culture. This inhibitory effect was not attributable to the induction of suppressor cells, as SDIF also inhibited the development of nonspecific suppressor cell activity in 7-day cultures of unstimulated spleen cells. The interleukine 2-dependent proliferation of cytotoxic T lymphocytes of or of blast cells was markedly reduced by the addition of SDIF. In contrast, the production of interleukine 2 itself was not impaired by SDIF. These results support the hypothesis of an inhibition by SDIF of a particular step of the mitotic cycle, probably posterior to the G₀-G₁ transition. An inhibitory activity of SDIF on the expression of the cytolytic activity of cytotoxic T lymphocytes was also observed.

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“…Cumulative evidence indicates that, among their diverse properties, interferons may have a regulatory influence on several immune functions: suppression of lymphocyte proliferation in response to mitogens and alloantigens (LindahlMagnusson et al, 1972a); inhibition in vivo and in vitro of antibody formation to T-cell-dependent and independent antigens (Braun & Levy, 1972;Gisler et al, 1974;Johnson et al, 1975;Sonnenfeld et al, 1977) and enhancement of specific cell-mediated cytotoxicity evoked by tumour-and allo-antigens (Lindahl et al, 1972b;Heron et al, 1976;Zarling et al, 1978). Interferon may also stimulate other effector-cell-mediated mechanisms such as phagocytosis (Huang et al, 1971;Donahoe & Huang, 1976) and nonspecific cytotoxicity (Schultz et al, 1977;Einhorn et al, 1978;Djeu et al, 1979;Senik et al, 1979), act directly on various cell types to inhibit their growth in vitro (Stewart et al, 1976;Balkwill et al, 1978) and modulate the expression of cell surface antigens on lymphocytes and tumour cells (Vignaux & Gresser, 1977).…”

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confidence: 99%

Enhancement of human natural cell-mediated cytotoxicity by interferon

Moore¹,

Potter²

1980

Br J Cancer

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Summary.-The effect of exogenous Namalva interferon (IF) on the natural killer (NK) cell activity of human blood lymphocytes was examined against 5 target cell lines (K562, CCRF/CEM, Molt 4, Raji and Bri8) using the 51Cr-release assay. Addition of IF to the test significantly increased the cytotoxicity, though not as much as when effector cells were treated with IF before the test. Augmentation of cytotoxicity was evident after only 1 h pretreatment and was maximal by 6 h. The rate of lysis of susceptible targets by IF-treated effectors markedly exceeded that by their untreated counterparts. Separation of lymphocyte subpopulations (by SRBC-rosette sedimentation and nylon-fibre column filtration) demonstrated that the activities of IF-stimulated and unstimulated cells were similarly distributed, suggesting that the major effect of IF is enhancement of the activity of pre-existing NK cells rather than generation of new populations of effectors. Target cell lines with high and low susceptibility to NK cells showed increased cytotoxicity by IF-treated effector cells. These findings may be relevant to the current discussion of the role of NK cells in immunosurveillance against neoplasia.

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Interferon inhibition of the primary in vitro antibody response to a thymus-independent antigen

Cited by 45 publications

References 17 publications

Regulation of the in vitro antibody response by neuroendocrine hormones

Regulation of the in vitro antibody response by neuroendocrine hormones

Inhibition of Cytotoxic T Lymphocytes by a Schistosome-Derived Inhibitory Factor Is Independent of an Inhibition of the Production of Interleukin 2

Enhancement of human natural cell-mediated cytotoxicity by interferon

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