A5047276561- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- HIV Research and Treatment
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- Prion Diseases and Protein Misfolding
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Reproductive System and Pregnancy
- Ubiquitin and proteasome pathways
- Virus-based gene therapy research
- Herpesvirus Infections and Treatments
- Neurological diseases and metabolism
- RNA Research and Splicing
- Immune Response and Inflammation
- HIV/AIDS Research and Interventions
- RNA and protein synthesis mechanisms
- Salivary Gland Disorders and Functions
- RNA regulation and disease
- Trace Elements in Health
- Animal Disease Management and Epidemiology
- Viral gastroenteritis research and epidemiology
- Viral Infectious Diseases and Gene Expression in Insects
- Bacteriophages and microbial interactions
University of Minnesota System
2004-2024
University of Minnesota
2014-2023
University of Minnesota Medical Center
2009
Emory University
2009
National Institute of Allergy and Infectious Diseases
2009
Johns Hopkins University Center for AIDS Research
2000
Great Lakes Institute of Management
2000
Middlesex Hospital
1989
Royal National Hospital for Rheumatic Diseases
1989
The inability of HIV-1-specific CTL to fully suppress virus replication as well the failure administration exogenous lower viral loads are not understood. To evaluate hypothesis that these phenomena due a localize at sites HIV-1 replication, we assessed distribution RNA and identified by peptide/HLA class I tetrameric complexes (tetramers) within lymph nodes 14 HIV-1-infected individuals who were receiving antiretroviral therapy. A median 0.04% follicular compared with 0.001% extrafollicular...
In the early stages of viral infection, outcomes depend on a race between expansion infection and immune response generated to contain it. We combined in situ tetramer staining with hybridization visualize, map, quantify relationships effector cells their targets tissues. simian immunodeficiency virus infections macaques lymphocytic choriomeningitis mice, magnitude timing establishment an excess versus were found correlate extent control outcome (i.e., clearance partial or poor persistent...
We previously demonstrated that HIV replication is concentrated in lymph node B cell follicles during chronic infection and HIV-specific CTL fail to accumulate large numbers at those sites. It unknown whether these observations can be generalized other secondary lymphoid tissues or virus compartmentalization occurs the absence of CTL. evaluated questions SIVmac239-infected rhesus macaques by quantifying SIV RNA(+) cells SIV-specific situ spleen, nodes, intestinal obtained several stages...
Significance Simian immunodeficiency virus (SIV)-specific follicular CD8 T cells represent a unique subset of antiviral that rapidly expand during pathogenic SIV infection, localize within B-cell follicles, and contribute to control chronic replication. The potential for these infiltrate sites ongoing viral replication persistence the ability induce by vaccination provide tremendous opportunity develop optimize therapeutic strategies target reduce HIV reservoirs in lymphoid tissues.
ABSTRACT In the acute stage of infection following sexual transmission human immunodeficiency virus (HIV) and simian (SIV), virus-specific CD8 + T-lymphocyte responses partially control but do not eradicate from lymphatic tissues (LTs) or prevent particularly massive depletion CD4 T lymphocytes in gut-associated tissue (GALT). We explored hypothetical explanations for this failure to clear loss SIV/rhesus macaque model intravaginal transmission. examined relationship between timing magnitude...
Staining Ag-specific T cells with fluorescently labeled tetrameric MHC/peptide complexes has provided a powerful experimental approach to characterizing the immune response. In this report, we describe an extension of method directly visualize in tissues. We successfully stained transgenic MHC tetramers spleen sections from both 2C and OT-1 TCR mice. addition, situ tetramer staining technique, detected very small population tissue after adoptive transfer syngeneic nontransgenic mouse. also...
ABSTRACT Cytotoxic T-lymphocyte (CTL) responses are thought to control human immunodeficiency virus replication during the acute phase of infection. Understanding CD8 + T-cell immune early after infection may, therefore, be important vaccine design. Analyzing these in humans is difficult since few patients diagnosed Additionally, infected by a variety viral subtypes, making it hard design reagents measure their acute-phase responses. Given complexities evaluating humans, we analyzed rhesus...
Abstract Human and simian immunodeficiency viruses (HIV SIV) exploit follicular lymphoid regions by establishing high levels of viral replication dysregulating humoral immunity. Follicular regulatory T cells (T FR ) are a recently characterized subset lymphocytes that influence the germinal centre response through interactions with helper FH ). Here, utilizing both human rhesus macaque models, we show impact HIV SIV infection on number function. We find proportionately numerically expand...
ABSTRACT Human immunodeficiency virus (HIV)- and simian (SIV)-specific CD8 + T cells are typically largely excluded from lymphoid B cell follicles, where HIV- SIV-producing most highly concentrated, indicating that follicles somewhat of an immunoprivileged site. To gain insights into virus-specific follicular cells, we determined the location phenotype SIV-specific in situ , local relationship these to Foxp3 effects depletion on levels chronically SIV-infected rhesus macaques. We found were...
There is a need to develop improved methods treat and potentially cure HIV infection. During chronic infection, replication concentrated within T follicular helper cells (Tfh) located B cell follicles, where low levels of virus-specific CTL permit ongoing viral replication. We previously showed that elevated SIV-specific in follicles are linked both decreased plasma loads. These findings provide the rationale strategy for targeting viral-producing using anti-viral chimeric antigen receptor...
During chronic human immunodeficiency virus (HIV) or simian (SIV) infection prior to AIDS progression, the vast majority of viral replication is concentrated within B cell follicles secondary lymphoid tissues. We investigated whether infusion T cells expressing an SIV-specific chimeric antigen receptor (CAR) and follicular homing receptor, CXCR5, could successfully kill viral-RNA+ in targeted SIV-infected rhesus macaques. In this study, CD4 CD8 from macaques were genetically modified express...
Abstract Background Transmissible spongiform encephalopathies (TSEs) or prion diseases are fatal neurodegenerative disorders which occur in humans and various animal species. Examples include Creutzfeldt-Jakob disease (CJD) humans, bovine encephalopathy (BSE) cattle, chronic wasting (CWD) deer elk, scrapie sheep, experimental mice. To gain insights into TSE pathogenesis, we made used cDNA microarrays to identify disease-associated alterations gene expression. Brain expression...
We sought design principles for a vaccine to prevent HIV transmission women by identifying correlates of protection conferred highly effective live attenuated SIV in the rhesus macaque animal model. show that SIVmac239Δnef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath mucosal epithelium female reproductive tract. The follicles produce IgG Abs reactive with viral envelope glycoprotein gp41 trimers, these are concentrated on path virus entry neonatal...
During chronic HIV infection, viral replication is concentrated in secondary lymphoid follicles. Cytotoxic CD8 T cells control extrafollicular regions, but not the follicle. Here, we show CXCR5hiCD44hiCD8 are a regulatory subset differing from conventional cells, and constitute majority of This subset, follicular (CD8 TFR), expand SIV exhibit enhanced expression Tim-3 IL-10, express less perforin compared to cells. TFR modestly limit helper (TFH), impair TFH IL-21 production via Tim-3,...
Tissue-resident memory (TRM) CD8+ T-cells are non-recirculating, long-lived cells housed in tissues that can confer protection against mucosal pathogens. Human immunodeficiency virus-1 (HIV-1) is a pathogen and the gastrointestinal tract an important site of viral pathogenesis transmission. Thus, TRM may be effector subset for controlling HIV-1 tissues. This study sought to determine abundance, phenotype, functionality context chronic infection. We found majority rectosigmoid were...
Despite the success of antiretroviral therapy (ART) to halt viral replication and slow disease progression, this treatment is not curative there remains an urgent need develop approaches clear latent HIV reservoir. The human IL-15 superagonist N-803 (formerly ALT-803) a promising anti-cancer biologic with potent immunostimulatory properties that has been extended into field as potential "shock kill" therapeutic for cure. However, ability reactivate virus modulate anti-viral immunity in vivo...
Spinocerebellar ataxia type 7 (SCA7) belongs to a group of neurological disorders caused by CAG repeat expansion in the coding region associated gene. To gain insight into pathogenesis SCA7 and possible functions ataxin-7, we examined subcellular localization ataxin-7 transfected COS-1 cells using cDNA clones with different tract lengths. In addition diffuse distribution throughout nucleus, nuclear matrix nucleolus. The location putative SCA7nuclear sequence (NLS) was confirmed fusing an...
ABSTRACT The presence, at the time of challenge, antiviral effector T cells in vaginal mucosa female rhesus macaques immunized with live-attenuated simian-human immunodeficiency virus 89.6 (SHIV89.6) is associated consistent and reproducible protection from pathogenic simian (SIV) challenge (18). Here, we definitively demonstrate protective role SIV-specific CD8 + T-cell response SHIV-immunized monkeys by lymphocyte depletion, an intervention that abrogated SHIV-mediated control replication...