Mechanisms by which Activated Macrophages Inhibit Lymphocyte Responses

Allison, A. C.

doi:10.1111/j.1600-065x.1978.tb00399.x

Cited by 208 publications

(66 citation statements)

References 99 publications

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“…Ail stages of N. dubius can activate complement by the alternative pathway (Prowse, Ey & Jenkin, 1979) so cleaving the complement component C, into C,a and C,b fragments, the latter of which is a potent agent for activating macrophages. Additionally the surface of many nematodes is polyanionic (Himmelhoch & Zuckerman, 1983;Murrell & Graham, 1983), a factor which can contribute to the activation of macrophages, and activated macrophages are known to be associated with chronic placation, such as occurs during infection with N. dubius (see Allison, 1978).…”

Section: Discussionmentioning

confidence: 99%

Suppression of heterologous immunity by Nematospiroides dubius antigens in vitro

Crawford

Behnke

Pritchard

1989

International Journal for Parasitology

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Section: Discussionmentioning

confidence: 99%

Suppression of heterologous immunity by Nematospiroides dubius antigens in vitro

Crawford

Behnke

Pritchard

1989

International Journal for Parasitology

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“…32 In tumour models, this is thought to contribute to tumour escape from immunosurveillance, but it is unlikely that this represents a normal physiological expression of this process. In inflammation stimulated by infection, restricting T-cell proliferation within the tissue could have a role simply by sparing finite metabolic resources for other effector cells that are present.…”

Section: Discussionmentioning

confidence: 99%

TNFR1 signalling is a critical checkpoint for developing macrophages that control of T‐cell proliferation

et al. 2010

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SummaryMacrophages (Mu) are professional antigen-presenting cells, but when they accumulate at sites of inflammation, they can inhibit T-cell proliferation. In experimental autoimmune uveoretinitis, this limits the expansion of T cells within the target organ. To define requirements for the elaboration of this outcome, we have generated populations of Mu in vitro that could also regulate T-cell responses; stimulating CD4 + T-cell activation and cytokine production, but simultaneously suppressing T-cell proliferation. When T cells are removed from the influence of such cells, normal T-cell responses are restored. We show that tumour necrosis factor 1 (TNFR1) signalling is a critical checkpoint in the development of such Mu, as TNFR1 )/) Mu are unable to suppress T-cell proliferation. This deficit in antigen-presenting cells results in a lack of production of prostaglandin E 2 (PGE 2 ) and nitric oxide, which are critical effector mechanisms that inhibit T-cell division. However, TNFR1 signalling is not required for the inhibitory function of Mu because we could circumvent the requirement for this receptor, by maturing Mu in the presence of exogenous interferon-c and PGE 2 . This produced TNFR1 )/) Mu that inhibited T-cell proliferation and indicates that TNFR1 delivers a signal that is necessary for the development but not the execution of this function.

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“…Interferons can be produced in response to various inducers by T and B cells (34), macrophages (35), and natural killer (NK) (36). The nature of the cell responsible for suppression and interferon production in this system remains unknown.…”

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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Mechanisms by which Activated Macrophages Inhibit Lymphocyte Responses

Cited by 208 publications

References 99 publications

Suppression of heterologous immunity by Nematospiroides dubius antigens in vitro

Suppression of heterologous immunity by Nematospiroides dubius antigens in vitro

TNFR1 signalling is a critical checkpoint for developing macrophages that control of T‐cell proliferation

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

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