Effects of SK&amp;F 105685, a novel anti-arthritic agent, on immune function in the dog

Kaplan, Johanne; Badger, Alison M.; Ruggieri, Elizabeth V.; Swift, Brandon; Bugelski, Peter J.

doi:10.1016/0192-0561(93)90087-f

Cited by 9 publications

(7 citation statements)

References 16 publications

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“…The existence of canine Treg cells has been surmised for several years, initially in studies of radiation chimaeras, 47 progressive myelopathy of German shepherd dogs 46 and the action of a novel anti-arthritic drug in beagles. 45 A population of canine CD4 + T cells with the phenotypic characteristics of Treg cells has been identified using an anti-mouse/rat Foxp3 mAb. [48][49][50][51][52] However, direct evidence of regulatory function has remained elusive until now.…”

Section: Discussionmentioning

confidence: 99%

“…24 44 However, relatively little is known about Treg cells in dogs, though indirect evidence for their existence has been available for several years. [45][46][47] We 48 and others [49][50][51][52][53][54] have used the anti-mouse/rat Foxp3 antibody clone FJK-16s to identify a population of canine CD4 + T cells that phenotypically resembles Treg cells, but direct evidence for regulatory activity has remained elusive. 55 In this study, we have characterized the phenotype and function of canine CD4 + CD25 high FOXP3 high T cells in vitro, providing direct evidence for the regulatory function of this T-cell subset in dogs -an important veterinary species that also serves as a model for several human diseases, including a number of cancers, [56][57][58] systemic lupus erythematosus 59,60 and several genetic diseases of the haemopoietic system.…”

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

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Phenotypic and functional characterization of a CD4+ CD25high FOXP3high regulatory T-cell population in the dog

et al. 2010

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Summary Relatively little is known about regulatory T (Treg) cells and their functional responses in dogs. We have used the cross‐reactive anti‐mouse/rat Foxp3 antibody clone FJK‐16s to identify a population of canine CD4+ FOXP3high T cells in both the peripheral blood (PB) and popliteal lymph node (LN). FOXP3+ cells in both PB and LN yielded positive staining with the newly developed anti‐murine/human Helios antibody clone 22F6, consistent with the notion that they were naturally occurring Treg cells. Stimulation of mononuclear cells of LN origin with concanavalin A (Con A) in vitro yielded increased proportions and median fluorescence intensity of FOXP3 expression by both CD4+ and CD8+ T cells. Removal of the Con A and continued culture disclosed a CD4+ FOXP3high population, distinct from the CD4+ FOXP3intermediate T cells; very few CD8+ FOXP3high T cells were observed, though CD8+ FOXP3intermediate cells were present in equal abundance to CD4+ FOXP3intermediate cells. The CD4+ FOXP3high T cells were thought to represent activated Treg cells, in contrast to the FOXP3intermediate cells, which were thought to be a more heterogeneous population comprising predominantly activated conventional T cells. Co‐staining with interferon‐γ (IFN‐γ) supported this notion, because the FOXP3high T cells were almost exclusively IFN‐γ−, whereas the FOXP3intermediate cells expressed a more heterogeneous IFN‐γ phenotype. Following activation of mononuclear cells with Con A and interleukin‐2, the 5% of CD4+ T cells showing the highest CD25 expression (CD4+ CD25high) were enriched in cells expressing FOXP3. These cells were anergic in vitro, in contrast to the 20% of CD4+ T cells with the lowest CD25 expression (CD4+ CD25−), which proliferated readily. The CD4+ CD25high FOXP3high T cells were able to suppress the proliferation of responder CD4+ T cells in vitro, in contrast to the CD4+ CD25− cells, which showed no regulatory properties.

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Section: Discussionmentioning

confidence: 99%

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

Phenotypic and functional characterization of a CD4+ CD25high FOXP3high regulatory T-cell population in the dog

et al. 2010

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“…Further studies documented the ability of the azaspirane drug SK&F 105685 to elicit suppressor cell activity in the spleen and bone marrow of healthy beagle dogs, putatively by the induction of 'suppressive T cells' [297,298]. The lack of global immunosuppression elicited by this drug suggested that it held promise as a future therapy for autoimmune disease [297].…”

Section: Regulatory T Cells In the Dog -What Do We Know?mentioning

confidence: 97%

All creatures great and small: regulatory T cells in mice, humans, dogs and other domestic animal species

Garden

Pinheiro

Cunningham

2011

International Immunopharmacology

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“…These (7,8). Azaspiranes induce nonspecific suppressor cell activity across numerous species, including rats, mice, and dogs (9,34 …”

Section: Nonspecific Immunity Modelmentioning

confidence: 99%

Single-Organism Model of Host Defense against Infection: A Novel Immunotoxicologic Approach to Evaluate Immunomodulatory Drugs

et al. 1997

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The immunotoxicologic effects of drugs on host defense have been studied widely using various animal models of infection. Here we describe a new approach to testing host defense by using a single organism ( Candida albicans ) in CBA/J mice. The model is configured to test 3 effector systems via different routes of inoculation to stimulate different effector arms of the immune response.Nonspecific immunity was evaluated by C. albicans colony-forming unit (CFU) count from the spleen at 2 hr (uptake) and ≥22 hr (clearance) following intravenous inoculation. Cell-mediated immunity was assessed by CFU count from an intramuscular injection site 6 days postinoculation. Humoral immunity was assessed by anti-Candida antibody titer, following multiple subcutaneous immunizations with C. albicans. Finally, overall immunity was evaluated following intravenous injection using survival as the endpoint. Histopathological, immunohistochemical, and electron microscopic evaluation of selected tissues revealed the involvement of the expected cell types in the different effector systems. Several immunomodulatory drugs—dexamethasone, cyclosporine, liposomal muramyltripeptide phosphatidylethanolamine, and SK&F 105685—were evaluated in the C. albicans model. Dexamethasone impaired host defense against C. albicans by suppressing all endpoints measured. Similarly, cyclosporine showed broad immunosuppressive activity, with the exception of yeast uptake from the spleen. In contrast, muramyl tripeptide-phosphatidylethanolamine enhanced all but cell-mediated immunity to C. albicans. SK&F 105685 displayed both stimulatory and inhibitory effects on immune responses to the infection. Our studies demonstrate that a single organism-based approach can be a useful method for evaluating the immunological hazards of drugs on host resistance to infection.

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Effects of SK&F 105685, a novel anti-arthritic agent, on immune function in the dog

Cited by 9 publications

References 16 publications

Phenotypic and functional characterization of a CD4+ CD25high FOXP3high regulatory T-cell population in the dog

Phenotypic and functional characterization of a CD4+ CD25high FOXP3high regulatory T-cell population in the dog

All creatures great and small: regulatory T cells in mice, humans, dogs and other domestic animal species

Single-Organism Model of Host Defense against Infection: A Novel Immunotoxicologic Approach to Evaluate Immunomodulatory Drugs

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