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1.
J Med Primatol ; 53(1): e12685, 2024 Feb.
Article de Anglais | MEDLINE | ID: mdl-38009978

RÉSUMÉ

BACKGROUND: The Vieira's titi monkey (Plecturocebus vieirai) was recently described and characterized as endemic to Brazil. According to the IUCN red list, this species is classified as critically endangered (CR). At the date of the publication of this manuscript, there are no published data on the health aspects of this species. METHODS: For this study, the necropsy, and histopathological data of the mortality of P. vieirai at Sorocaba Zoo (São Paulo, Brazil) were collected and analyzed. RESULTS: Causes of death diagnosed included disorders of the urinary, gastrointestinal, immune, and circulatory systems. CONCLUSIONS: This study provides information regarding the pathological conditions of P. vieirai and points to urinary and gastrointestinal diseases as the main causes of death in this species at Sorocaba Zoo. These results can help veterinarians who have this species under their care diagnose and deal with it more quickly, increasing the probability of survival.


Sujet(s)
Callicebus , Pitheciidae , Animaux , Espèce en voie de disparition , Études rétrospectives , Brésil/épidémiologie
2.
Vaccines (Basel) ; 11(12)2023 Dec 18.
Article de Anglais | MEDLINE | ID: mdl-38140266

RÉSUMÉ

A Bacille Calmette-Guérin (BCG) is still the only licensed vaccine for the prevention of tuberculosis, providing limited protection against Mycobacterium tuberculosis infection in adulthood. New advances in the delivery of DNA vaccines by electroporation have been made in the past decade. We evaluated the safety and immunogenicity of the DNA-hsp65 vaccine administered by intramuscular electroporation (EP) in cynomolgus macaques. Animals received three doses of DNA-hsp65 at 30-day intervals. We demonstrated that intramuscular electroporated DNA-hsp65 vaccine immunization of cynomolgus macaques was safe, and there were no vaccine-related effects on hematological, renal, or hepatic profiles, compared to the pre-vaccination parameters. No tuberculin skin test conversion nor lung X-ray alteration was identified. Further, low and transient peripheral cellular immune response and cytokine expression were observed, primarily after the third dose of the DNA-hsp65 vaccine. Electroporated DNA-hsp65 vaccination is safe but provides limited enhancement of peripheral cellular immune responses. Preclinical vaccine trials with DNA-hsp65 delivered via EP may include a combination of plasmid cytokine adjuvant and/or protein prime-boost regimen, to help the induction of a stronger cellular immune response.

3.
J Comp Neurol ; 531(13): 1276-1298, 2023 09.
Article de Anglais | MEDLINE | ID: mdl-37279778

RÉSUMÉ

Nonhuman primates (NHPs) are important to study the pathophysiology of neurodegenerative disease and evaluate therapies targeting the central nervous system (CNS). Understanding the age-associated incidence of natural CNS pathology in a given NHP species is critical to assess the safety of potential treatments for neurodegenerative disorders like Alzheimer's disease (AD). We describe background and age-related neuropathology in the St. Kitts African green monkey (AGM), a recognized translational model for neurodegenerative research, additionally defining the age progression of AD-associated neuropathology in this species. Seventy-one AGM brains were examined, representing age groups of 3-6 years (n = 20), 7-9 years (n = 20), 10-15 years (n = 20), and >15 years (n = 11). A subset of brains (n = 31) was assessed immunohistochemically for AD-related pathology, including expressions of Aß, tau, and GFAP. Age-related microscopic findings included hemosiderosis, spheroid formation, neuronal lipofuscinosis and neuromelanosis, white matter and neuropil vacuolation, astrocytosis, and focal microgliosis. Non-age-related findings included perivascular ceroid-laden macrophages, meningeal melanosis, and vascular mineralization. Immunohistochemistry revealed 4G8-immunopositive Aß plaques and vascular deposits in the prefrontal, frontal, cingulate, and temporal cortices of nine animals over 15 years of age, with associated increase in GFAP expression. In 12 animals, 11 over the age of 10 years, phosphorylated tau CP13-immunoreactive neurons, neuropil, and oligodendrocyte-like cells were seen in the prefrontal, frontal, cingulate, orbital, temporal, and entorhinal cortices as well as the hippocampus; no neurofibrillary tangles were observed. AD-related pathology showed an age-related development in cognitive-associated areas in the AGM, highlighting the value of the AGM as a natural model for these neurodegenerative diseases.


Sujet(s)
Maladie d'Alzheimer , Maladies neurodégénératives , Animaux , Chlorocebus aethiops , Maladie d'Alzheimer/anatomopathologie , Protéines tau/métabolisme , Peptides bêta-amyloïdes , Maladies neurodégénératives/métabolisme , Maladies neurodégénératives/anatomopathologie , Encéphale/métabolisme , Vieillissement/anatomopathologie
4.
J Med Primatol ; 52(2): 131-134, 2023 04.
Article de Anglais | MEDLINE | ID: mdl-36377612

RÉSUMÉ

Increases of soluble urokinase plasminogen activator receptor (suPAR) were measured in both urine and plasma of a Chlorocebus aethiops (African green monkey; AGM) mucosal infected with SARS-CoV-2. The data indicate that elevated suPAR may be associated with renal dysfunction and pathology in the context of COVID-19.


Sujet(s)
COVID-19 , Maladies du rein , Animaux , Chlorocebus aethiops , COVID-19/complications , Récepteurs à l'activateur du plasminogène de type urokinase , SARS-CoV-2 , Marqueurs biologiques
5.
Ciênc. rural (Online) ; 53(4): e20210866, 2023. graf
Article de Anglais | LILACS-Express | VETINDEX | ID: biblio-1384588

RÉSUMÉ

ABSTRACT: We described a case of fatal septicemic yersiniosis in a young adult brown titi monkey (Plecturocebus brunneus) which presented lethargy and severe anemia. Postmortem external assessment revealed marked dehydration and pale pink mucous membranes. The main gross findings included enlarged liver with yellow pinpoints, enlarged spleen with yellow nodules, mucosal ulcerations in the large intestine, enlarged mesenteric lymph nodes, and pulmonary hemorrhage. Histology revealed necrosuppurative hepatosplenitis with intralesional colonies of rod-shaped gram-negative bacteria, ulcerative colitis, reactive lymphoid hyperplasia, and fibrinous and hemorrhagic pneumonia. Bacterial culture and identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry confirmed the diagnosis of yersiniosis by Yersinia enterocolitica. This study indicated that yersiniosis should be considered as a differential diagnosis of death in brown titi monkeys.


RESUMO: Descrevemos um caso de yersiniose septicêmica fatal em um zogue-zogue (Plecturocebus brunneus) jovem adulto que apresentava um quadro de letargia e anemia severa. Macroscopicamente, havia acentuada desidratação e as mucosas estavam pálidas. Notou-se hepatomegalia com múltiplos pontos amarelos e esplenomegalia com múltiplos nódulos amarelos pelo parênquima. Ainda, ulcerações da mucosa do intestino grosso, linfonodos mesentéricos aumentados e hemorragia pulmonar foram observados. A avaliação histológica revelou hepatite e esplenite necrossupurativas associadas a agregados bacterianos bacilares gram-negativos intralesionais, colite ulcerativa, hiperplasia linfoide reativa e pneumonia fibrino-hemorrágica. A cultura bacteriana e identificação através do método de espectrometria de massa por ionização e dessorção a laser assistida por matriz associada ao tempo de voo confirmou o diagnóstico de yersiniose por Yersinia enterocolitica. Este estudo demonstra que a yersiniose deve ser considerada como um diagnóstico diferencial de causa de morte em zogue-zogues.

6.
Ciênc. rural (Online) ; 53(4): 1-5, 2023. ilus
Article de Anglais | VETINDEX | ID: biblio-1412798

RÉSUMÉ

We described a case of fatal septicemic yersiniosis in a young adult brown titi monkey (Plecturocebus brunneus) which presented lethargy and severe anemia. Postmortem external assessment revealed marked dehydration and pale pink mucous membranes. The main gross findings included enlarged liver with yellow pinpoints, enlarged spleen with yellow nodules, mucosal ulcerations in the large intestine, enlarged mesenteric lymph nodes, and pulmonary hemorrhage. Histology revealed necrosuppurative hepatosplenitis with intralesional colonies of rod-shaped gram-negative bacteria, ulcerative colitis, reactive lymphoid hyperplasia, and fibrinous and hemorrhagic pneumonia. Bacterial culture and identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry confirmed the diagnosis of yersiniosis by Yersinia enterocolitica. This study indicated that yersiniosis should be considered as a differential diagnosis of death in brown titi monkeys.


Descrevemos um caso de yersiniose septicêmica fatal em um zogue-zogue (Plecturocebus brunneus) jovem adulto que apresentava um quadro de letargia e anemia severa. Macroscopicamente, havia acentuada desidratação e as mucosas estavam pálidas. Notou-se hepatomegalia com múltiplos pontos amarelos e esplenomegalia com múltiplos nódulos amarelos pelo parênquima. Ainda, ulcerações da mucosa do intestino grosso, linfonodos mesentéricos aumentados e hemorragia pulmonar foram observados. A avaliação histológica revelou hepatite e esplenite necrossupurativas associadas a agregados bacterianos bacilares gram-negativos intralesionais, colite ulcerativa, hiperplasia linfoide reativa e pneumonia fibrino-hemorrágica. A cultura bacteriana e identificação através do método de espectrometria de massa por ionização e dessorção a laser assistida por matriz associada ao tempo de voo confirmou o diagnóstico de yersiniose por Yersinia enterocolitica. Este estudo demonstra que a yersiniose deve ser considerada como um diagnóstico diferencial de causa de morte em zogue-zogues.


Sujet(s)
Animaux , Primates , Yersinia enterocolitica/pathogénicité , Yersinioses/médecine vétérinaire , Pitheciidae , Maladies des singes
7.
Parasit Vectors ; 15(1): 23, 2022 Jan 10.
Article de Anglais | MEDLINE | ID: mdl-35012637

RÉSUMÉ

BACKGROUND: Yellow fever virus (YFV) is an arbovirus that, despite the existence of a safe and effective vaccine, continues to cause outbreaks of varying dimensions in the Americas and Africa. Between 2017 and 2019, Brazil registered un unprecedented sylvatic YFV outbreak whose severity was the result of its spread into zones of the Atlantic Forest with no signals of viral circulation for nearly 80 years. METHODS: To investigate the influence of climatic, environmental, and ecological factors governing the dispersion and force of infection of YFV in a naïve area such as the landscape mosaic of Rio de Janeiro (RJ), we combined the analyses of a large set of data including entomological sampling performed before and during the 2017-2019 outbreak, with the geolocation of human and nonhuman primates (NHP) and mosquito infections. RESULTS: A greater abundance of Haemagogus mosquitoes combined with lower richness and diversity of mosquito fauna increased the probability of finding a YFV-infected mosquito. Furthermore, the analysis of functional traits showed that certain functional groups, composed mainly of Aedini mosquitoes which includes Aedes and Haemagogus mosquitoes, are also more representative in areas where infected mosquitoes were found. Human and NHP infections were more common in two types of landscapes: large and continuous forest, capable of harboring many YFV hosts, and patches of small forest fragments, where environmental imbalance can lead to a greater density of the primary vectors and high human exposure. In both, we show that most human infections (~ 62%) occurred within an 11-km radius of the finding of an infected NHP, which is in line with the flight range of the primary vectors. CONCLUSIONS: Together, our data suggest that entomological data and landscape composition analyses may help to predict areas permissive to yellow fever outbreaks, allowing protective measures to be taken to avoid human cases.


Sujet(s)
Brésil , Culicidae , Épidémies de maladies , Vecteurs moustiques , Fièvre jaune/transmission , Aedes/croissance et développement , Aedes/virologie , Animaux , Biodiversité , Brésil/épidémiologie , Climat , Culicidae/croissance et développement , Culicidae/virologie , Forêts , Humains , Vecteurs moustiques/classification , Vecteurs moustiques/croissance et développement , Vecteurs moustiques/virologie , Facteurs de risque , Fièvre jaune/épidémiologie
8.
Ecohealth ; 18(4): 414-420, 2021 12.
Article de Anglais | MEDLINE | ID: mdl-34843021

RÉSUMÉ

In 2019, a new coronavirus disease (COVID-19) was detected in China. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was capable to infect domestic and captive mammals like cats, tigers and minks. Due to genetic similarities, concern about the infection of non-human primates (NHPs) and the establishment of a sylvatic cycle has grown in the Americas. In this study, neotropical primates (NP) were sampled in different areas from Brazil to investigate whether they were infected by SARS-CoV-2. A total of 89 samples from 51 NP of four species were examined. No positive samples were detected via RT-qPCR, regardless of the NHP species, tissue or habitat tested. This work provides the first report on the lack of evidence of the circulation of SARS-CoV-2 in NP. The expansion of wild animals sampling is necessary to understand their role in the epidemiology of SARS-CoV-2 and other potentially zoonotic pathogens in natural environments shared by humans.


Sujet(s)
COVID-19 , Pandémies , Animaux , Brésil , Humains , Primates , SARS-CoV-2
9.
Viruses ; 13(10)2021 10 16.
Article de Anglais | MEDLINE | ID: mdl-34696518

RÉSUMÉ

Since the explosive outbreak of Zika virus in Brazil and South/Central America in 2015-2016, the frequency of infections has subsided, but Zika virus remains present in this region as well as other tropical and sub-tropical areas of the globe. The most alarming aspect of Zika virus infection is its association with severe birth defects when infection occurs in pregnant women. Understanding the mechanism of Zika virus pathogenesis, which comprises features unique to Zika virus as well as shared with other teratogenic pathogens, is key to future prophylactic or therapeutic interventions. Nonhuman primate-based research has played a significant role in advancing our knowledge of Zika virus pathogenesis, especially with regard to fetal infection. This review summarizes what we have learned from these models and potential future research directions.


Sujet(s)
Macaca/virologie , Infection par le virus Zika/métabolisme , Infection par le virus Zika/anatomopathologie , Animaux , Brésil/épidémiologie , Amérique centrale/épidémiologie , Modèles animaux de maladie humaine , Épidémies de maladies , Femelle , Grossesse , Complications infectieuses de la grossesse/virologie , Virus Zika/pathogénicité , Infection par le virus Zika/virologie
10.
Am J Primatol ; 83(2): e23229, 2021 02.
Article de Anglais | MEDLINE | ID: mdl-33464603

RÉSUMÉ

Personality in animals has been extensively researched in recent decades. Temporal consistency of behaviors is almost always part of the personality definition and is usually explored in several different testing sessions or observation periods. However, it is still unclear whether the obtained personality constructs are stable across several years, which might be especially important for long-living animals, such as primates. Further, little is known on whether the personality structures obtained in the laboratory reflect the structures obtained under ecologically relevant conditions in the wild. Therefore, we conducted a battery of personality tests on common marmosets (Callithrix jacchus) (N = 27), compared it with a test battery conducted 4 years beforehand on a subset of animals in captivity (N = 13) and ran an adapted version under field conditions at Baracuhy Biological Field Station, Brazil (N = 18). Under captive conditions, we found a remarkably similar personality structure across 4 testing years. Further, we found high long-term temporal consistency in the first two personality components, Boldness and Exploration; however, monkeys that changed their social (i.e., breeding) status between the two testing periods showed a significant increase in Boldness scores. Under field conditions, we found a somewhat similar personality structure as compared to the laboratory, which to some extent corroborates ecological validity of our personality test design. Nevertheless, whether the structure in the wild is suppressed or expanded in comparison to captivity, and in which way the social setting influences personality structure, should be further explored. Taken together, our results contribute to the discussion about the reliability and ecological validity of personality structures in nonhuman primates.


Sujet(s)
Comportement animal , Callithrix/psychologie , Personnalité , Animaux , Brésil , Écosystème , Femelle , Mâle , Reproductibilité des résultats , Comportement social , Facteurs temps
11.
J Virol ; 92(16)2018 08 15.
Article de Anglais | MEDLINE | ID: mdl-29875247

RÉSUMÉ

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus with devastating outcomes seen recently in the Americas due to the association of maternal ZIKV infection with fetal microcephaly and other fetal malformations not previously associated with flavivirus infections. Here, we have developed the olive baboon (Papio anubis) as a nonhuman primate (NHP) translational model for the study of ZIKV pathogenesis and associated disease outcomes to contrast and compare with humans and other major NHPs, such as macaques. Following subcutaneous inoculation of adult male and nonpregnant female baboons, viremia was detected at 3 and 4 days postinfection (dpi) with the concordant presentation of a visible rash and conjunctivitis, similar to human ZIKV infection. Furthermore, virus was detected in the mucosa and cerebrospinal fluid. A robust ZIKV-specific IgM and IgG antibody response was also observed in all the animals. These data show striking similarity between humans and the olive baboon following infection with ZIKV, suggesting our model is a suitable translational NHP model to study ZIKV pathogenesis and potential therapeutics.IMPORTANCE ZIKV was first identified in 1947 in a sentinel rhesus monkey in Uganda and subsequently spread to Southeast Asia. Until 2007, only a small number of cases were reported, and ZIKV infection was relatively minor until the South Pacific and Brazilian outbreaks, where more severe outcomes were reported. Here, we present the baboon as a nonhuman primate model for contrast and comparison with other published animal models of ZIKV, such as the mouse and macaque species. Baboons breed year round and are not currently a primary nonhuman primate species used in biomedical research, making them more readily available for studies other than human immunodeficiency virus studies, which many macaque species are designated for. This, taken together with the similarities baboons have with humans, such as immunology, reproduction, genetics, and size, makes the baboon an attractive NHP model for ZIKV studies in comparison to other nonhuman primates.


Sujet(s)
Anticorps antiviraux/métabolisme , Modèles animaux de maladie humaine , Virémie/diagnostic , Infection par le virus Zika/diagnostic , Virus Zika/pathogénicité , Animaux , Brésil , Femelle , Humains , Immunoglobuline G/métabolisme , Immunoglobuline M/métabolisme , Mâle , Muqueuse/virologie , Papio , Virémie/liquide cérébrospinal , Virus Zika/immunologie , Infection par le virus Zika/liquide cérébrospinal , Infection par le virus Zika/immunologie
12.
J Med Primatol ; 47(2): 124-127, 2018 04.
Article de Anglais | MEDLINE | ID: mdl-29193137

RÉSUMÉ

We report the pathological, immunohistochemical, and molecular features of fatal acute systemic toxoplasmosis in an adult, female, free-living southern muriqui (Brachyteles arachnoides) from São Paulo state, Brazil. PCR-RFLP genotyping analysis identified the #21 genotype of Toxoplasma gondii. This represents the first report of acute toxoplasmosis involving this genotype in humans and animals.


Sujet(s)
Atelinae , Maladies des singes/diagnostic , Toxoplasma/physiologie , Toxoplasmose animale/diagnostic , Animaux , Brésil , Issue fatale , Femelle , Maladies des singes/anatomopathologie , Toxoplasma/génétique , Toxoplasmose animale/anatomopathologie
14.
Am J Transplant ; 17(6): 1476-1489, 2017 Jun.
Article de Anglais | MEDLINE | ID: mdl-28009481

RÉSUMÉ

Systemic administration of autologous regulatory dendritic cells (DCreg; unpulsed or pulsed with donor antigen [Ag]), prolongs allograft survival and promotes transplant tolerance in rodents. Here, we demonstrate that nonhuman primate (NHP) monocyte-derived DCreg preloaded with cell membrane vesicles from allogeneic peripheral blood mononuclear cells induce T cell hyporesponsiveness to donor alloantigen (alloAg) in vitro. These donor alloAg-pulsed autologous DCreg (1.4-3.6 × 106 /kg) were administered intravenously, 1 day before MHC-mismatched renal transplantation to rhesus monkeys treated with costimulation blockade (cytotoxic T lymphocyte Ag 4 immunoglobulin [CTLA4] Ig) and tapered rapamycin. Prolongation of graft median survival time from 39.5 days (no DCreg infusion; n = 6 historical controls) and 29 days with control unpulsed DCreg (n = 2), to 56 days with donor Ag-pulsed DCreg (n = 5) was associated with evidence of modulated host CD4+ and CD8+ T cell responses to donor Ag and attenuation of systemic IL-17 production. Circulating anti-donor antibody (Ab) was not detected until CTLA4 Ig withdrawal. One monkey treated with donor Ag-pulsed DCreg rejected its graft in association with progressively elevated anti-donor Ab, 525 days posttransplant (160 days after withdrawal of immunosuppression). These findings indicate a modest but not statistically significant beneficial effect of donor Ag-pulsed autologous DCreg infusion on NHP graft survival when administered with a minimal immunosuppressive drug regimen.


Sujet(s)
Cellules dendritiques/immunologie , Survie du greffon/immunologie , Isoantigènes/immunologie , Défaillance rénale chronique/chirurgie , Transplantation rénale , Lymphocytes T/immunologie , Donneurs de tissus , Animaux , Agranulocytes , Macaca mulatta , Mâle , Tolérance à la transplantation , Transplantation homologue
16.
Am J Transplant ; 16(10): 2994-3006, 2016 10.
Article de Anglais | MEDLINE | ID: mdl-27217298

RÉSUMÉ

Transforming growth factor ß1 (TGFß1) plays a key role in T cell homeostasis and peripheral tolerance. We evaluated the influence of a novel human mutant TGFß1/Fc (human IgG4 Fc) fusion protein on memory CD4+ and CD8+ T cell (Tmem) responses in vitro and their recovery following antithymocyte globulin (ATG)-mediated lymphodepletion in monkeys. TGFß1/Fc induced Smad2/3 protein phosphorylation in rhesus and human peripheral blood mononuclear cells and augmented the suppressive effect of rapamycin on rhesus Tmem proliferation after either alloactivation or anti-CD3/CD28 stimulation. In combination with IL-2, the incidence of CD4+ CD25hi Foxp3hi regulatory T cells (Treg) and Treg:Th17 ratios were increased. In lymphodepleted monkeys, whole blood trough levels of infused TGFß1/Fc were maintained between 2 and 7 µg/mL for 35 days. Following ATG administration, total T cell numbers were reduced markedly. In those given TGFß1/Fc infusion, CD8+ T cell recovery to predepletion levels was delayed compared to controls. Additionally, numbers of CD4+ CD25hi CD127lo Treg increased at 4-6 weeks after depletion but subsequently declined to predepletion levels by 12 weeks. In all monkeys, CD4+ CD25hi Foxp3hi Treg/CD4+ IL-17+ cell ratios were reduced, particularly after stopping TGFß1/Fc infusion. Thus, human TGFß1/Fc infusion may delay Tmem recovery following lymphodepletion in nonhuman primates. Combined (low-dose) IL-2 infusion may be required to improve the Treg:Th17 ratio following lymphodepletion.


Sujet(s)
Homéostasie/immunologie , Mémoire immunologique/immunologie , Déplétion lymphocytaire/effets indésirables , Récepteur Fc/métabolisme , Lymphocytes T régulateurs/immunologie , Facteur de croissance transformant bêta-1/métabolisme , Animaux , Humains , Agranulocytes/immunologie , Macaca mulatta , Mâle , Récepteur Fc/génétique , Facteur de croissance transformant bêta-1/génétique
17.
Am J Transplant ; 16(2): 661-71, 2016 Feb.
Article de Anglais | MEDLINE | ID: mdl-26372923

RÉSUMÉ

Increasing evidence from small animal models shows that myeloid-derived suppressor cells (MDSCs) can play a crucial role in inhibiting allograft rejection and promoting transplant tolerance. We identified CD3(-)CD20(-)HLA-DR(-)CD14(+)CD33(+)CD11b(+) cells in peripheral blood of healthy rhesus macaques. These putative monocytic MDSCs constituted 2.1% ± 1.7% of lin(-)HLA-DR(-) peripheral blood mononuclear cells. Administration of granulocyte-macrophage colony-stimulating factor (CSF) and granulocyte CSF increased their incidence to 5.3% ± 3.4%. The total number of MDSCs that could be flow sorted from a single whole rhesus leukapheresis product was 38 ± 13 × 10(6) (n = 10 monkeys). Freshly isolated or cryopreserved MDSCs from mobilized monkeys incorporated in cultures of anti-CD3- and anti-CD28-stimulated autologous T cells markedly suppressed CD4(+) and CD8(+) T cell proliferation and cytokine secretion (interferon γ, IL-17A). Moreover, these MDSCs enhanced CD4(+)CD25(hi)Foxp3(+) regulatory T cell (Treg) expansion while inhibiting proliferation of activated memory T cells and increasing Treg relative to effector and terminally differentiated memory T cells. Inhibition of arginase-1, but not inducible nitric oxide synthase activity, partially reversed the inhibitory effect of the MDSCs on CD8(+) T cell proliferation. Consequently, functional MDSCs can be isolated from nonhuman primates for prospective use as therapeutic cellular vaccines in transplantation.


Sujet(s)
Lymphocytes T CD4+/immunologie , Lymphocytes T CD8+/immunologie , Monocytes/immunologie , Cellules myéloïdes/immunologie , Lymphocytes T régulateurs/immunologie , Animaux , Arginase/métabolisme , Lymphocytes T CD4+/métabolisme , Lymphocytes T CD8+/métabolisme , Prolifération cellulaire , Cytokines/métabolisme , Études de faisabilité , Facteur de stimulation des colonies de granulocytes/métabolisme , Facteur de stimulation des colonies de granulocytes et de macrophages/métabolisme , Humains , Leucaphérèse , Activation des lymphocytes , Macaca mulatta , Mâle , Monocytes/métabolisme , Cellules myéloïdes/métabolisme , Lymphocytes T régulateurs/métabolisme
18.
Am J Transplant ; 16(7): 1999-2015, 2016 07.
Article de Anglais | MEDLINE | ID: mdl-26700196

RÉSUMÉ

The ability of regulatory T cells (Treg) to prolong allograft survival and promote transplant tolerance in lymphodepleted rodents is well established. Few studies, however, have addressed the therapeutic potential of adoptively transferred, CD4(+) CD25(+) CD127(-) Foxp3(+) (Treg) in clinically relevant large animal models. We infused ex vivo-expanded, functionally stable, nonselected Treg (up to a maximum cumulative dose of 1.87 billion cells) into antithymocyte globulin-lymphodepleted, MHC-mismatched cynomolgus monkey heart graft recipients before homeostatic recovery of effector T cells. The monkeys also received tacrolimus, anti-interleukin-6 receptor monoclonal antibodies and tapered rapamycin maintenance therapy. Treg administration in single or multiple doses during the early postsurgical period (up to 1 month posttransplantation), when host T cells were profoundly depleted, resulted in inferior graft function compared with controls. This was accompanied by increased incidences of effector memory T cells, enhanced interferon-γ production by host CD8(+) T cells, elevated levels of proinflammatory cytokines, and antidonor alloantibodies. The findings caution against infusion of Treg during the early posttransplantation period after lymphodepletion. Despite marked but transient increases in Treg relative to endogenous effector T cells and use of reputed "Treg-friendly" agents, the host environment/immune effector mechanisms instigated under these conditions can perturb rather than favor the potential therapeutic efficacy of adoptively transferred Treg.


Sujet(s)
Lymphocytes T CD8+/immunologie , Rejet du greffon/immunologie , Transplantation cardiaque , Mémoire immunologique/immunologie , Alloanticorps/immunologie , Lymphocytes T régulateurs/immunologie , Tolérance à la transplantation/immunologie , Transfert adoptif , Allogreffes , Animaux , Survie du greffon , Déplétion lymphocytaire , Macaca fascicularis
19.
Am J Transplant ; 15(5): 1253-66, 2015 May.
Article de Anglais | MEDLINE | ID: mdl-25783759

RÉSUMÉ

Ex vivo-expanded cynomolgus monkey CD4(+)CD25(+)CD127(-) regulatory T cells (Treg) maintained Foxp3 demethylation status at the Treg-specific demethylation region, and potently suppressed T cell proliferation through three rounds of expansion. When carboxyfluorescein succinimidyl ester- or violet proliferation dye 450-labeled autologous (auto) and nonautologous (non-auto)-expanded Treg were infused into monkeys, the number of labeled auto-Treg in peripheral blood declined rapidly during the first week, but persisted at low levels in both normal and anti-thymocyte globulin plus rapamycin-treated (immunosuppressed; IS) animals for at least 3 weeks. By contrast, MHC-mismatched non-auto-Treg could not be detected in normal monkey blood or in blood of two out of the three IS monkeys by day 6 postinfusion. They were also more difficult to detect than auto-Treg in peripheral lymphoid tissue. Both auto- and non-auto-Treg maintained Ki67 expression early after infusion. Sequential monitoring revealed that adoptively transferred auto-Treg maintained similarly high levels of Foxp3 and CD25 and low CD127 compared with endogenous Treg, although Foxp3 staining diminished over time in these nontransplanted recipients. Thus, infused ex vivo-expanded auto-Treg persist longer than MHC-mismatched non-auto-Treg in blood of nonhuman primates and can be detected in secondary lymphoid tissue. Host lymphodepletion and rapamycin administration did not consistently prolong the persistence of non-auto-Treg in these sites.


Sujet(s)
Sous-unité alpha du récepteur à l'interleukine-2/métabolisme , Sous-unité alpha du récepteur à l'interleukine-7/métabolisme , Lymphocytes T régulateurs/immunologie , Animaux , Sérum antilymphocyte/composition chimique , Facteurs de transcription Forkhead/métabolisme , Haplotypes , Immunosuppresseurs/composition chimique , Antigène KI-67/métabolisme , Macaca fascicularis , Complexe majeur d'histocompatibilité , Mâle , Méthylation , Phénotype , Sirolimus/composition chimique
20.
Ecohealth ; 12(2): 288-97, 2015 Jun.
Article de Anglais | MEDLINE | ID: mdl-25515075

RÉSUMÉ

The Mycobacterium tuberculosis complex causes tuberculosis in humans and nonhuman primates and is a global public health concern. Standard diagnostics rely upon host immune responses to detect infection in nonhuman primates and lack sensitivity and specificity across the spectrum of mycobacterial infection in these species. We have previously shown that the Oral Swab PCR (OSP) assay, a direct pathogen detection method, can identify the presence of M. tuberculosis complex in laboratory and free-ranging Old World monkeys. Addressing the current limitations in tuberculosis diagnostics in primates, including sample acquisition and pathogen detection, this paper furthers our understanding of the presence of the tuberculosis-causing bacteria among New World monkeys in close contact with humans. Here we use the minimally invasive OSP assay, which includes buccal swab collection followed by amplification of the IS6110 repetitive nucleic acid sequence specific to M. tuberculosis complex subspecies, to detect the bacteria in the mouths of Peruvian New World monkeys. A total of 220 buccal swabs from 16 species were obtained and positive amplification of the IS6110 sequence was observed in 30 (13.6%) of the samples. To our knowledge, this is the first documentation of M. tuberculosis complex DNA in a diverse sample of Peruvian Neotropical primates.


Sujet(s)
Techniques bactériologiques/méthodes , Tuberculose/diagnostic , Tuberculose/médecine vétérinaire , Facteurs âges , Animaux , ADN bactérien , ADN mitochondrial , Femelle , Mâle , Maladies des singes , Mycobacterium/génétique , Pérou , Platyrrhini/microbiologie , Réaction de polymérisation en chaîne , Tuberculose/épidémiologie
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