Maclean A.G.,Tulane National Primate Research Center Covington |
Walker E.,Tulane National Primate Research Center Covington |
Sahu G.K.,Roger William Medical Center Providence |
Skowron G.,Roger William Medical Center Providence |
And 4 more authors.
Journal of Medical Primatology | Year: 2014
Background: To increase the immunosurveillance in HIV infection, we used retroviral vectors expressing CD4-chimeric antigen receptors (CARs) to genetically modify autologous T cells and redirect CTL toward HIV. The CD4 extracellular domain targets envelope and the intracellular signaling domains activate T cells. The maC46 fusion inhibitor binds HIV and blocks viral replication. Methods: We stimulated rhesus PBMCs with antibodies to CD3/CD28 and cotransduced T cells with CD4-CAR and maC46 vectors. CD4-CAR-transduced T cells were added to Env+ 293T cells at E:T of 1:1. Killing of target cells was measured as reduced impedance. Results: We observed gene expression in 60-70% of rhesus CD3+CD8+ T cells with the individual vectors and in 35% of the cells with both vectors. CD4-CAR-transduced populations specifically killed Env+ cells. Conclusions: In these studies, we showed that designer T cells were redirected to kill Env+ cells. Control of viremia without HAART would revolutionize treatment for HIV patients. © 2014 John Wiley & Sons A/S.
PubMed | Tulane National Primate Research Center Covington, Tulane University and Texas A&M University
Type: | Journal: Frontiers in cellular and infection microbiology | Year: 2013
Brucella melitensis, a bacterial pathogen and agent of epizootic abortion causes multiple pathologies in humans as well as a number of agriculturally important animal species. Clinical human brucellosis manifests as a non-specific, chronic debilitating disease characterized by undulant fever, arthropathies, cardiomyopathies and neurological sequelae. These symptoms can occur acutely for a few weeks or persist for months to years. Within the brain, endothelial and glial cells can be infected leading to downstream activation events including matrix metalloprotease (MMP) and cytokine secretion and Toll-like receptor (TLR) signaling. These events are likely to lead to tissue remodeling, including morphologic changes in neuronal and glial cells, which are linked to neurological complications including depressive behavior, immune activation and memory loss. Our hypothesis was that B. melitensis infection and neurobrucellosis would lead to activation of astrocytes through upregulation of TLR2 and stimulate concurrent changes in the microanatomy. All six animals were infected via inhalation route. TLR2 expression was approximately doubled in white matter astrocytes of infected rhesus macaques. There was also a 50% increase in the number of astrocytes per unit area in subcortical white matter tracts suggesting increased innate immune activation. This coincided with dramatic increases in the length and complexity of the cell arbor of hypertrophic astrocytes in both cortical gray and white matter. Thus, aerosol-induced brucellosis results in dramatically increased innate immune activation of astrocytes in the absence of widespread neuroinflammation.
PubMed | Tulane National Primate Research Center Covington
Type: Journal Article | Journal: Animal welfare (South Mimms, England) | Year: 2010
Human interaction as environmental enrichment for chimpanzees (Pan troglodytes) and other primates is widely promoted and believed to be of value, but has been subject to little objective evaluation. This study assessed the effects of positive human interaction (eg relaxed treat feeding, playing, and other forms of social interaction compatible with personnel safety) on the behaviour of adult chimpanzees. Subjects were housed indoors in groups of two or three individuals. The level of interaction during routine care and management (ie in the process of cleaning, feeding, and monitoring) represented the baseline condition. The test condition involved a familiar caretaker spending an additional 10 minutes per day, 5 days a week, with each chimpanzee. This study was designed to assess carry-over effects of interaction on behaviour outside of the context of care staff presence. Therefore, in all phases of the study, data (97 hours of focal animal sampling) were collected only when caretakers were absent from the building. During the increased human interaction phase, the chimpanzees groomed each other more and showed lower levels of the following behaviours: regurgitation/reingestion, other oral abnormal behaviours, inactivity, and reactivity to the displays of neighboring groups. A trend toward reduced agonistic displaying was detected as well. Attempted interactions with the observer shifted significantly from predominantly aggressive to predominantly affiliative in nature. These results suggest that simple, unstructured affiliation between humans and chimpanzees should be a valued component of behavioural management.