Genetically‐restricted effector molecules released by human lymphocytes in response to early pregnancy factor

Rolfe, Barbara E.; Quinn, Kathryn; Athanasas, Stavrosia; Cavanagh, Alice; Morton, H. Craig

doi:10.1038/icb.1989.31

Cited by 18 publications

(11 citation statements)

References 11 publications

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“…Previous studies have shown that the oviduct, during oestrus and early pregnancy, produces an inhibitor, 55 , 56 which modifies the response of EPF in the rosette inhibition test 54 . In its presence, higher concentrations of EPF are required to stimulate release of lymphokines by which the action of EPF in the rosette inhibition test and the delayed‐type hypersensitivity (DTH) reaction is mediated 57 , 58 . The range of concentrations over which EPF is able to affect lymphocytes is thus extended, suggesting a possible biological function for the inhibitor.…”

Section: Nature Of the Early Pregnancy Factor Molecule And Factors Afmentioning

confidence: 99%

“…The immunosuppressive action of EPF is mediated through the sequential induction of lymphokines. Rolfe et al have described two lymphokines, EPF‐S 1 and EPF‐S 2 , induced from both human and mouse lymphocytes 57 , 58 , 85 . The activity of both factors is genetically restricted, a property that clearly distinguishes them from the inducing EPF, which is neither strain nor species restricted.…”

Section: Early Pregnancy Factor Induces Genetically Restricted Lymphomentioning

confidence: 99%

“…Different cell populations are involved in production of EPF‐S 1 and EPF‐S 2 , with EPF‐S 1 having the ability to induce EPF‐S 2 but not vice versa 85 . Restriction of activity of EPF‐S 1 has been mapped to the I region of the murine H‐2 57 and to HLA‐DR in humans, 58 while that of EPF‐S 2 is localized to the Igh region 85 . In mice, spleen cells producing EPF‐S 1 and those responding to it shared identity at either I‐A, I‐B or I‐J subregions, 57 and EPF‐S 2 (but not EPF‐S 1 ) carries the I‐J determinant 85 .…”

Section: Early Pregnancy Factor Induces Genetically Restricted Lymphomentioning

confidence: 99%

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Early pregnancy factor: An extracellular chaperonin 10 homologue

Morton

1998

Immunol Cell Biol

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Summary Early pregnancy factor (EPF) has been identi®ed as a homologue of chaperonin 10 (cpn10) with immunosuppressive and growth factor properties. As a homologue of cpn10, it belongs to the heat shock family of proteins (hsp) but, unlike other members of this family, EPF is detected extracellularly. Early pregnancy factor was ®rst discovered in pregnancy serum by the rosette inhibition test, and the novelty of its discovery was that its presence could diagnose pregnancy within 6±24 h of a fertile mating. As well as being a monitor of the presence of a viable embryo, it is necessary for embryonic survival. In this capacity it acts as both an immunosuppressant and growth factor. Early pregnancy factor is also a product of proliferating primary and neoplastic cells and functions as an autocrine growth factor both in vivo and in vitro. It has a modifying e ect on the outcome of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Early pregnancy factor is considered to be one of the major factors involved in the modi®cation of multiple sclerosis observed during pregnancy.

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Section: Nature Of the Early Pregnancy Factor Molecule And Factors Afmentioning

confidence: 99%

Section: Early Pregnancy Factor Induces Genetically Restricted Lymphomentioning

confidence: 99%

Section: Early Pregnancy Factor Induces Genetically Restricted Lymphomentioning

confidence: 99%

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Early pregnancy factor: An extracellular chaperonin 10 homologue

Morton

1998

Immunol Cell Biol

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“…In vivo , it suppresses the delayed‐type hypersensitivity (DTH) response 12 , 13 , prolongs skin graft survival time 14 and suppresses clinical signs of experimental autoimmune encephalomyelitis (EAE) 11 , 13 , the animal model of multiple sclerosis (MS). Suppression of the DTH response is induced by soluble mediators released from lymphocytes following EPF binding 15 , 16 . Thus, EPF displays the regulated production and pleiotropic function typical of many cytokines and growth factors.…”

Section: Introductionmentioning

confidence: 99%

Investigation of the immunocompetent cells that bind early pregnancy factor and preliminary studies of the early pregnancy factor target molecule

et al. 2004

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Summary Early pregnancy factor (EPF) is a secreted protein with immunosuppressive and growth factor properties. It has been shown to suppress the delayed-type hypersensitivity response in mice as well as acute and chronic forms of experimental autoimmune encephalomyelitis in rats and mice, respectively. In previous studies, we have demonstrated that EPF binds to a population of lymphocytes and we hypothesized that it mediates its suppressive effects by binding to CD4 + T cells. In the present study, we isolated monocytes and subpopulations of lymphocytes and labelled them with fluoresceinated EPF in order to determine which populations bind EPF. We demonstrated that EPF binds specifically to CD4 + , CD8 + , CD14 + (monocytes) and CD56 + NK cells but not to CD19 + B cells. The identity of the molecule(s) on the cell surface that is targeted by EPF is unknown, but as EPF is an extracellular homologue of the intracellular protein chaperonin 10 (Cpn10), we examined the possibility that the EPF receptor is a membrane-associated form of chaperonin 60 (Cpn60), the functional associate of Cpn10 within the cell. The EPF target molecule on lymphocytes was visualized by chemical cross-linking of exogenous iodinated Cpn10 to cells and probed with anti-Cpn60. The effect of anti-Cpn60 on activity in the EPF bioassay, the rosette inhibition test, was also examined. In both instances, no specific interaction of this antibody and the putative receptor was observed. It was concluded that the cell surface molecule targeted by EPF is unlikely to be a homologue of Cpn60.

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“…The cell pellet PI, produced by incubation of spleen cells with pregnancy serum or its active consti¬ tuent EPF, after washing to remove the inducing stimulus, provides the ALS-enhancing effect measured by the bioassay (Morton et ai, 1976). Rolfe et al (1988Rolfe et al ( , 1989 have shown that, at this point, the active agents are soluble suppressor factors produced in response to pregnancy serum or EPF by a small population of cells in the spleen cell suspension. By incubating PI in HBSS alone for a further 0-5 h and collecting the subsequent supernatant S2, Orozco et ai (1990) and Clarke et ai (1990) removed the inducing signal (EPF) and collected suppressor factors and any soluble mediators produced in response to them.…”

Section: Discussionmentioning

confidence: 97%

Relationship between early pregnancy factor, mouse embryo-conditioned medium and platelet-activating factor

Cavanagh

Rolfe²,

Athanasas‐Platsis³

et al. 1991

Reproduction

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The effects of synthetic platelet-activating factor (PAF-acether) and mouse embryo-conditioned medium (a source of embryo-derived PAF (EPAF)) on production of early pregnancy factor (EPF) were compared. Embryo-conditioned medium, itself inactive in the EPF bioassay, stimulated ovarian production of EPF in vitro but PAF-acether did not. In vivo, embryo-conditioned medium induced EPF activity in serum of oestrous female, but not in male, mice in contrast to PAF-acether, which induced activity in serum of both male and female mice. This PAF-induced activity was transitory, declining significantly by 2 h and disappearing by 3 h after injection. Activity induced by embryo-conditioned medium was first evident at 2 h after injection, serum concentrations increasing up to 6 h after injection. By discriminating between the behaviour of PAF-acether and EPAF, these studies reinforce the conclusions of other workers that the molecule produced by the embryo is not PAF. Further investigations into the mechanism of action of PAF-acether revealed that it is a potent inducer of activity in the EPF bioassay, with an absolute requirement for platelets in the spleen cell suspension used in the assay. This platelet-derived active species was bound specifically by an anti-EPF monoclonal antibody, indicating that it is EPF-like. This is consistent with parallel studies showing that platelets are not required for induction of activity by either pregnancy serum or purified EPF. These studies were applied to the PAF-induced leukotriene-like species, which had been found by others to be active in the EPF bioassay. Pregnancy serum induced the appearance of this substance from the spleen cell suspension used in the assay; thus the leukotriene-like substance may be regarded as an effector molecule in vitro or mediator of the initiating stimulus of EPF in the bioassay.

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Genetically‐restricted effector molecules released by human lymphocytes in response to early pregnancy factor

Cited by 18 publications

References 11 publications

Early pregnancy factor: An extracellular chaperonin 10 homologue

Early pregnancy factor: An extracellular chaperonin 10 homologue

Investigation of the immunocompetent cells that bind early pregnancy factor and preliminary studies of the early pregnancy factor target molecule

Relationship between early pregnancy factor, mouse embryo-conditioned medium and platelet-activating factor

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