Suppression of bovine T- and B-lymphocyte responses by fetuin, a bovine glycoprotein

Splitter, Gary A.; Everlith, K M

doi:10.1016/0008-8749(82)90322-7

Cited by 14 publications

(3 citation statements)

References 22 publications

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“…In the experiments reported here, the mechanisms of collaboration between bovine macrophages and T lymphocytes in response to killed B. abortus 1119 have been investigated. Few studies have examined bovine lymphocyte responses to B. abortius (2,36). Results of the present study indicate a biphasic response at various bacterial concentrations and times.…”

Section: Discussionmentioning

confidence: 48%

Collaboration of bovine T lymphocytes and macrophages in T-lymphocyte response to Brucella abortus

Splitter¹,

Everlith²

1986

Infect Immun

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Brucella abortus-induced bovine macrophage-T-lymphocyte collaboration was studied as a prerequisite for the eventual clearance of this infectious organism. Esterase-positive, peripheral blood monocytes functioned as an adherent antigen-presenting cell population. A dual requirement for expression of bacterial antigens in combination with self major histocompatibility complex class II products was required by adherent cells for the activation of T lymphocytes. Comparison of antigen-presenting cell populations that were either trypsinized or nontrypsinized following B. abortus ingestion substantiated the need for phagocytosis and antigen processing. A monoclonal antibody (H4) directed against major histocompatibility complex class II determinants was able to block or, with complement, to abrogate T-lymphoctye responses. Measurement of both proliferation and interleukin 2 production via [3H]thymidine incorporation confirmed specific activation of an enriched T-lymphocyte population. These results indicate that in vivo-primed T lymphocytes of peripheral blood origin recognize phagocytized bacterial components of the facultative intracellular bacterium B. abortus and may contribute to the removal of the bacteria. Furthermore, bovine peripheral blood-adherent cells function as classic antigen-presenting cells, which suggests that macrophages are capable of processing this bacteria. Therefore, any lymphocyte-mediated dysfunction attributable to B. abortus most likely occurs at some point in the cascade of immune events following initial macrophage-T-lymphocyte collaboration.

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Section: Discussionmentioning

confidence: 48%

Collaboration of bovine T lymphocytes and macrophages in T-lymphocyte response to Brucella abortus

Splitter¹,

Everlith²

1986

Infect Immun

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“…Lymphocyte proliferation assays with a murine model have been used extensively to answer questions on T-cell specificity (8,11), macrophage-T-cell interactions (35,36), lymphokine biology (21,29), and the frequency of T-cell precursors of a given specificity (26,27). Proliferative assays with bovine lymphoid cells have been used to answer questions on the general immune state of animals (12,32,34), but in general the assay conditions and cellular interactions have not been as well defined as those in the murine or human systems. The lymphocyte proliferative assay described in this study is very similar to that described (11,18).…”

Section: Discussionmentioning

confidence: 99%

Suppression of antigen- and mitogen-induced proliferation of bovine lymphocytes by excretory-secretory products of Oesophagostomum radiatum

Gasbarre¹,

Romanowski²,

Douvres³

1985

Infect Immun

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Excretory-secretory products (ESP) isolated from in vitro-grown stage-3 to -4 larvae of Oesophagostomum radiatum were found to inhibit both the in vitro antigen-specific proliferation of keyhole limpet hemocyaninand ovalbumin-primed lymphocytes and the proliferation induced by the T-cell mitogen concanavalin A. As little as 50 ng of ESP protein per culture resulted in 50% reductions of subsequent proliferative responses. Antigen-induced responses were 100 to 1,000 times more sensitive to inhibition than were mitogen-induced responses. The inhibitory activity was found to affect the induction of proliferation as evidenced by the observation that complete inhibition was seen when ESP were added to cultures within the first 24 h. ESP were found to have no inhibitory activity when added 72 h after the initiation of the cultures. The inhibition was not a result of a direct action upon macrophages because pulsing of adherent cells with ESP had no more effect on a subsequent proliferative response than did a pulsing of the culture vessel itself. The inhibitory activity eluted from high-pressure liquid chromatography columns in the same fractions as protein standards with molecular weights of 25,000 to 35,000. Of special interest is the fact that this inhibitor of the expansion of immunoreactive clones of lymphocytes is found associated with the stages of parasites most initimately associated with host tissues, namely larval stages 3 and 4. Many parasitic infections have been shown to exert strong immunoregulatory effects upon the host. In many cases, this immunoregulation has been shown at the level of either the host immune response to immunization with defined antigens or the response to infection by unrelated infectious agents. Examples of immunoregulation at the systemic level have been demonstrated after infection with a number of parasite species (3,10,16,28). In contrast, little is known about the regulation by parasites at the cellular level of the host immune response. African trypanosomes have been shown to suppress specific antitrypanosome in vitro T-cell responses (18,19). This suppression was found to affect both the T-cell and macrophage components of the response (19), and that responsiveness could be at least partially restored by the addition to the culture of supernatants of activated T cells (20).Oesophagostomum radiatum is a nematode which infects the distal small intestine, cecum, and proximal colon of cattle. After the infective larvae are ingested in contaminated herbage, they penetrate the mucosa of the distal ileum and then undergo a complex development in the submucosa, leading to a marked inflammation at the sites of development. This inflammation results in the formation of large nodules, accounting for the common name of the parasite, the nodular worm of cattle. Recent advances in large-scale in vitro cultivation of 0. radiatum make it possible to obtain relatively synchronous populations of advanced stages from infective larvae through young adults (15). These techniques permit both the iso...

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“…It contains complex oligosaccharides buts its core peptide displays significant homology between the many different species in which it has been identified. The principal physiological role of fetuin remains unknown, but it has been reported to be involved in cell growth (Nie, 1992;Ohnishi et al, 1997), fatty acid transport (Cayatte el al., 1990), bone mineralisation (Schinke et al, 1996), haematopoiesis (White et al, 1993), immune responses (Splitter and Everlith, 1982), monocyte phagocytosis (Lewis and Andre, 1981) and chemotaxis i Malone and Richards, 1987), TGF-P receptor binding (Demetriou et al, 1996), and protease inhibition (Yamamoto and Sinohara, 1993).…”

Section: Labelled Fetuin Binds To the Cell Surfacementioning

confidence: 99%

Regulation of Macrophage Phagocytosis of Apoptotic Cells by CD44

Hart

2001

Clinical Science

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Development of effective therapeutic strategies for inflammatory diseases requires understanding of the cellular and molecular mechanisms that determine whether inflammation resolves or progresses to scarring and tissue destruction. Apoptosis of neutrophil granulocytes is an important determinant of the resolution of inflammation, providing a mechanism for down-regulation of function and triggering "silent" clearance by phagocytes of potentially destructive inflammatory cells. However, if the rate of cell death by apoptosis is such that macrophage clearance capacity is exceeded, apoptotic cells may progress to secondary necrosis, resulting in release of harmful cellular contents and damage to the surrounding tissue. Changes in the composition of the extracellular matrix in response to tissue injury may influence macrophage phagocytic capacity. In particular, adhesion of macrophages to fibronectin significantly augmented their capacity for phagocytosis of apoptotic neutrophils, an effect that may involve |31 integrins and other cellular receptors. The aim of this thesis was to investigate the role of CD44, a surface molecule that is expressed by many cell types including human monocytes and alveolar macrophages, in the phagocytosis of apoptotic neutrophils in vitro. Expression of CD44 by human monocyte-derived macrophages was characterised by indirect immunofluorescence and flow cytometry, and by immunoprecipitation and Western blotting. A well characterised phagocytic assay was used to assess the role of macrophage CD44 in the phagocytosis of apoptotic neutrophils in vitro. Data presented in this thesis demonstrate that pre-incubation of human monocyte-derived macrophages with CD44 monoclonal antibody 5A4 resulted in an average 2.3-fold increase in the proportion of macrophages that phagocytosed one or more apoptotic neutrophils across a range of basal phagocytosis rates, whereas control antibody had no effect. In contrast, incubation of macrophages with CD44 antibody had no demonstrable effect on phagocytosis of immunoglobulin-opsonized erythrocytes or zymosan, suggesting that CD44 ligation had specifically influenced the phagocyte machinery involved in the binding and/or engulfment of apoptotic cells. These data provide the first evidence that macrophage phagocytosis of apoptotic neutrophils can be rapidly (within minutes) augmented following ligation of specific macrophage surface receptors. CD44 ligation by antibody 5A4 had no effect on macrophage release of interleukin-8, interleukin-10, or tumour necrosis factor-a, consistent with clearance of apoptotic cells by a "non-inflammatory" mechanism. Use of bivalent F(ab')2 and monovalent Fab' fragments demonstrated a requirement for cross-linking of CD44. A panel of ligands and antibodies that bind to relevant macrophage surface receptors was used to investigate whether CD44 ligation recruited previously defined mechanisms to augment phagocytosis of apoptotic neutrophils. However, none of the agents tested had any demonstrable inhibitory effect upon CD44augmented...

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Suppression of bovine T- and B-lymphocyte responses by fetuin, a bovine glycoprotein

Cited by 14 publications

References 22 publications

Collaboration of bovine T lymphocytes and macrophages in T-lymphocyte response to Brucella abortus

Collaboration of bovine T lymphocytes and macrophages in T-lymphocyte response to Brucella abortus

Suppression of antigen- and mitogen-induced proliferation of bovine lymphocytes by excretory-secretory products of Oesophagostomum radiatum

Regulation of Macrophage Phagocytosis of Apoptotic Cells by CD44

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