Mechanisms of Activation of Human Natural Killer Cells Against Tumor and Virus‐infected Cells

Santoli, Daniela; Koprowski, Hilary

doi:10.1111/j.1600-065x.1979.tb00269.x

Cited by 173 publications

(67 citation statements)

References 88 publications

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“…Clearly, interferons possess antiviral activity, and the inability of lymphocytes from MS patients to produce these factors could contribute to the persistence of virus in the central nervous system. More intriguing, however, are recent observations showing that natural killer cells, which are non-T, non-B lymphocytes responsible for spontaneous cytotoxicity against tumor cells (39), play an important role in the cytolysis of virus-infected cells (40,41). In addition, administration of interferon or interferon inducers in vivo and in vitro enhances the cytolytic activity of natural killer cells (42,43).…”

Section: Discussionmentioning

confidence: 99%

Absence of virus-induced lymphocyte suppression and interferon production in multiple sclerosis

Neighbour

Bloom

1979

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

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Lymphocytes from normal adult donors exposed in vitro to inactivated measles virus were found to exert significant suppression (33.9%) of the concanavalin A responses of cryopreserved, autochthonous responder cells. In marked contrast, lymphocytes from multiple sclerosis patients exhibited significantly reduced suppression (1.5%), and in 80% of cases failed to suppress at all. The degree of suppression increased slightly with age of the patient but did not vary with the clinical stage of disease. There was no apparent genetic restriction of suppressor activity. Although specificity of this phenomenon for measles virus has not been established, no differences in the responses of lymphocytes from normal or multiple sclerosis patient donors were found with subacute sclerosing panencephalitis, Sendai, canine distemper, mumps, or influenza viruses.Supernates of measles-treated lymphocytes from normal donors possessed both suppressive and antiviral activities. Both activities were resistant to pH 2 treatment and were neutralized by an anti-human leukocyte interferon antiserum, strongly suggesting that interferon (probably type I) was the mediator of suppression. Consistent with their inability to suppress concanavalin A responses, lymphocytes from multiple sclerosis patients failed to produce significant amounts of interferon in response to measles challenge in vitro. These results extend previous observations that multiple sclerosis patients are unable to respond appropriately to measles virus antigen in vitro. The etiology and pathogenesis of multiple sclerosis (MS), a slow neurological disease of man, remain unknown. Epidemiological and serological studies have suggested that an infectious agent might be responsible for this disease (reviewed in ref. 1). Measles virus has received perhaps the most attention as a consequence of the observation of increased measles antibodies in the sera and cerebrospinal fluids of MS patients (2) and the isolation of a measles-like virus from the brain and lymph nodes of patients with another slow neurological disease, subacute sclerosing panencephalitis (SSPE) (3,4 In the present study, we have investigated the in vitro antigen-specific induction of suppressor activity in lymphocytes from normal adult and MS patient donors, using measles virus.Our results show that, in response to measles challenge, lymphocytes from MS patients exhibit an almost total absence of suppressor activity. In addition, they fail to produce significant amounts of a soluble immunosuppressive and antiviral factor which appears to be interferon. MATERIALS AND METHODSLymphocyte Donors. Lymphocytes were separated, by Ficoll-Paque (Pharmacia) density gradient centrifugation, from 50 ml of heparinized blood drawn from the following groups of donors: normal adults (mean age, 35 yr; laboratory personnel); MS patients (mean age, 40 yr) who were diagnosed by a board-certified neurologist as having "clinically definite" MS according to the criteria of Schumacher et al. (12); patients with cerebrovascular dise...

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Section: Discussionmentioning

confidence: 99%

Absence of virus-induced lymphocyte suppression and interferon production in multiple sclerosis

Neighbour

Bloom

1979

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

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“…Influence ofAsbestos Exposure on Nonspecific Inmmunity: Natural Killer Cells Natural killer cells are a unique lymphocyte population with the ability to rapidly lyse tumor cells independent of major histocompatibility complex gene products (16) and are thought to be the first line of defense against cancer cells or virally infected cells (17,18).…”

Section: Introductionmentioning

confidence: 99%

Selected new developments in asbestos immunotoxicity.

Rosenthal¹,

Corsini²,

Simeonova³

1998

Environ Health Perspect

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Research over the past three decades has shown that the mammalian immune system can be altered by the occupational exposure of asbestos. Early clinical studies generally focused on systemic observations of immune alteration such as the number and function of peripheral lymphocytes and monocytes. More recently as the regulatory influence of local immunity in health and disease becomes more defined, immunologic changes occurring in the lung, the primary target organ of asbestos, have been significant areas of investigation. This review will focus on recent studies that examine the influence of asbestos on pulmonary immunity as well as the role of host immune competence in asbestos-related disease. -Environ Health Perspect 106(Suppl 1):159-169 (1998). http://ehpnetl.niehs.nih.gov/docs/1998/Suppl-1/159-169rosenthal/abstract.html

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“…NK cells lack the features of mature T cells, B cells, or macrophages (1, 2, 4), though a portion of human NK cells binds weakly to sheep erythrocytes, suggesting an association with T cells (5). Most NK cells in human peripheral blood bear Fc receptors, but natural killing is not primarily dependent on antibody nor on the Fc receptor (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Natural killing of tumor cells by human peripheral blood cells. Suppression of killing in vitro by tumor-promoting phorbol diesters.

Seaman¹,

Gindhart²,

Blackman³

et al. 1981

J. Clin. Invest.

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A B S T R A C T Tumor-promoting phorbol diesters were shown to suppress natural killing in vitro by human peripheral blood mononuclear cells. The inhibitory effect of different phorbol diesters and their analogues correlated with their potency as tumor promoters, the most effective agent being 12-0-tetradecanoylphorbol-13-acetate (TPA). Both peripheral blood cells and targets specifically bound TPA, and natural killing could be inhibited by pretreatment of either cell population with TPA, though this was less effective than direct addition of TPA to the assay. Cells that had been pretreated with TPA released TPA and metabolites of TPA during subsequent incubation in fresh medium. This release of TPA was evidently responsible for the inhibition of natural killing by pretreated target cells; in experiments where labeled and unlabeled target cells were mixed, pretreatment of unlabeled targets with TPA inhibited killing of labeled targets. Suppression of natural killing by TPA was greatly reduced when adherent cells were removed from the peripheral blood cells, suggesting that monocytes mediate suppression. Inhibition of natural killing by TPA provides a model for examining the regulation of natural killing. Suppression of natural killing by phorbol diesters may contribute to their activity as tumor promoters.

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Mechanisms of Activation of Human Natural Killer Cells Against Tumor and Virus‐infected Cells

Cited by 173 publications

References 88 publications

Absence of virus-induced lymphocyte suppression and interferon production in multiple sclerosis

Absence of virus-induced lymphocyte suppression and interferon production in multiple sclerosis

Selected new developments in asbestos immunotoxicity.

Natural killing of tumor cells by human peripheral blood cells. Suppression of killing in vitro by tumor-promoting phorbol diesters.

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