The immunosuppressive effect of type II mouse interferon preparations on antibody production

Sonnenfeld, Gerald; Mandel, Adrian D.; Merigan, Thomas C.

doi:10.1016/0008-8749(77)90243-x

Cited by 145 publications

(38 citation statements)

References 16 publications

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“…Interferons in vitro (20)(21)(22)(23)(24). For this reason, supernates of measles-treated lymphocytes from both donor groups were assayed for antiviral activity.…”

Section: Methodsmentioning

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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“…Interferons in vitro (20)(21)(22)(23)(24). For this reason, supernates of measles-treated lymphocytes from both donor groups were assayed for antiviral activity.…”

Section: Methodsmentioning

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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“…Furthermore, interferon inhibits the growth of tumor cells in vitro or of transplanted and chemically induced tumors in animals (14). Against such a background, Sonnenfeld et al (33) reported that type II interferon was 250 times more active than type I in immunosuppression of antibody production in mice. Similar results were reported by Glasgow et al (personal communication) who used systems of murine osteogenic sarcoma and murine type I or type II interferon in mice.…”

Section: Characterization Of Antiviral Actioity Induced By Ssmmentioning

confidence: 99%

Interferon‐Inducing Activity of an Immuno‐therapeutic Anticancer Agent, SSM, Prepared from Mycobacterium tuberculosis Strain Aoyama B

Hayashi

Ebina

Suzuki

et al. 1981

Microbiology and Immunology

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The interferon-inducing capacity of arabinornannan-lipid preparation (SSM) extracted from Mycobacterium tuberculosis Aoyama B in both BCG-sensitized and unsensitized mice was studied in comparison with that of purified protein derivative (PPD) prepared from the same tubercle bacillus. Although it is known that PPD cannot stimulate interferon production in BCG-unsensitized mice, interferon activity was found in sera of both groups of mice after intravenous injection of SSM at a dose of 5 mg/kg. The maximum titer was detected 5 hr after injection. The interferon induced by SSM in both groups of mice shared certain physicochemical properties with the immune interferon induced by PPD in BCGsensitized mice. In BCG-unsensitized mice, interferon induction by SSM was markedly inhibited by pretreatment with trypan blue and carrageenan, whereas it was not depressed in BCG-sensitized mice given the same treatment or when interferon was induced by PPD. In addition, induction of interferon in BCGsensitized mice by SSM and PPD and in unsensitized mice by SSM was completely abrogated by pretreatment with hydrocortisone acetate and whole-body x-irradiation (700 R). These results suggest that in BCG-unsensitized mice macrophages, in addition to X-ray or hydrocortisone-sensitive cells, may be required for interferon induction by SSM.

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“…Interferon and its inducers have been associated with other effects which depend upon many specific and non-specific mechanisms of host defence (Hilleman, 1970;Baron, 1973;Johnson & Baron, 1976;Sonnenfeld et al, 1977;Gresser, 1977). Thus, interferons have been considered as alternatives to immunization and as factors in the control of virus virulence or enhancement of protection against virulent challenge.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Interferon and Double-stranded RNA upon the Virus-Host Interaction: Studies with Togavirus Strains in Mice

Bradish¹,

Titmuss

1981

Journal of General Virology

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The immunosuppressive effect of type II mouse interferon preparations on antibody production

Cited by 145 publications

References 16 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

Interferon‐Inducing Activity of an Immuno‐therapeutic Anticancer Agent, SSM, Prepared from Mycobacterium tuberculosis Strain Aoyama B

The Effects of Interferon and Double-stranded RNA upon the Virus-Host Interaction: Studies with Togavirus Strains in Mice

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