A5041900263- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Virus-based gene therapy research
- Cancer Research and Treatments
- Occupational and environmental lung diseases
- Cancer Immunotherapy and Biomarkers
- Viral Infections and Outbreaks Research
- Mosquito-borne diseases and control
- Cancer Cells and Metastasis
- Diabetes and associated disorders
- Immune cells in cancer
- Myasthenia Gravis and Thymoma
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- Listeria monocytogenes in Food Safety
- Biopolymer Synthesis and Applications
- Toxin Mechanisms and Immunotoxins
- Viral Infections and Vectors
- vaccines and immunoinformatics approaches
- Chronic Myeloid Leukemia Treatments
- thermodynamics and calorimetric analyses
- PI3K/AKT/mTOR signaling in cancer
- Syphilis Diagnosis and Treatment
Rush University Medical Center
2013-2024
University Medical Center
2021
Rush University
2011-2018
UConn Health
2001-2007
Jenner Institute
2007
The University of Western Australia
1987-2003
Harry Perkins Institute of Medical Research
2003
Queen Elizabeth II Medical Centre
1987-2001
Graduate School USA
1997
Princess Margaret Cancer Centre
1988
Many intracellular pathogens infect a broad range of host tissues, but the importance T cells for immunity in these sites is unclear because most our understanding antimicrobial cell responses comes from analyses lymphoid tissue. Here, we show that response to viral or bacterial infection, antigen-specific CD8 migrated nonlymphoid tissues and were present as long-lived memory cells. Strikingly, isolated exhibited effector levels lytic activity directly ex vivo, contrast their splenic...
Abstract Cross-presentation of cell-bound Ags from established, solid tumors to CD8 cells is efficient and likely have a role in determining host response tumor. A number investigators predicted that when tumor are derived apoptotic either no response, due Ag “sequestration,” or cross-tolerance would ensue. Because the crucial issue whether this happens vivo has never been addressed, we induced apoptosis established hemagglutinin (HA)-transfected AB1 BALB/c mice using apoptosis-inducing...
Significance Immunotherapy has revolutionized cancer treatment, yielding unprecedented long-term responses and survival. However, a significant proportion of patients remain refractory, which correlates with the absence immune-infiltrated (“hot”) tumors. Here, we observed that FDA-approved unadjuvanted seasonal influenza vaccines administered via intratumoral injection not only provide protection against active virus lung infection, but also reduce tumor growth by increasing antitumor CD8 +...
Abstract The intestinal mucosal CD8 T cell response to infection with Listeria monocytogenes was measured using MHC class I tetramers and compared the in peripheral blood, secondary lymphoid tissue, liver. To assess vaccination potential of analyze responses C57BL/6 mouse strains, a recombinant expressing OVA (rLM-ova) generated. peaked at 9 days postinfection much larger fraction mucosa liver pool specific, as spleen. However, these differences were not linked bacterial titers each site....
Abstract A number of tumor studies have indicated a link between CD4 help and the magnitude persistence CTL activity; however, mechanisms underlying this been largely unclear. To evaluate determine by which CD4+ T cells synergize with CD8+ to prevent growth, we used novel technique monitoring in vivo labeling target CFSE. This approach was supported direct visualization using peptide-MHC tetramers follow tumor-specific cells. The data presented demonstrate that while cotransfer Ag-specific...
Abstract Following activation within secondary lymphoid tissue, CD8 T cells must migrate to targets, such as infected self allografts, and tumors, mediate contact-dependent effector functions. To test whether the pattern of migration activated was dependent on site Ag encounter, we examined distribution mouse Ag-specific following local challenges. Our findings indicated that migrated pervasively all nonlymphoid organs irrespective initial engagement. Using an adoptive transfer system,...
Abstract Tumor growth is rarely associated with a strong specific CTL response, suggesting that the immune system ignorant of presence tumor because Ags are not readily available to or sequestered from potential effector cells. We studied in vivo activation naive TCR transgenic hemagglutinin (HA)-specific CD8+ T cells adoptively transferred into mice bearing HA-expressing using 5,6-carboxy-succinimidyl-fluorescein-ester labeling, which allows identification proliferating HA-specific...
Abstract The role of CD4 T cells in providing help to CD8 primary and secondary responses infection remains controversial. Using recombinant strains virus bacteria expressing the same Ag, we determined requirement for endogenous cell with vesicular stomatitis Listeria monocytogenes (LM). Depletion had no effect on frequency or virus-specific either lymphoid nonlymphoid tissues. In contrast, LM-specific response was dependent. Surprisingly, recall also dependent, which correlated a CD40/CD40L...
ABSTRACT We examined the interactions of live and lysed spirochetes with innate immune cells. THP-1 monocytoid cells were activated to comparable extents by Borrelia burgdorferi B. Treponema pallidum lysates but poorly T. . Because internalized spirochetes, we turned an ex vivo peripheral blood mononuclear cell system that would more closely reflect spirochete-mononuclear phagocyte occur during actual infection. In this system, induced significantly greater monocyte activation inflammatory...
Abstract Mucosal tissues are subject to frequent pathogen exposure and major sites for transmission of infectious disease. CD8 T cells play a critical role in controlling mucosa-acquired infections even though their migration into mucosal is tightly regulated. The mechanisms signals that control the formation tissue-resident memory poorly understood; however, one key regulator cell differentiation, mammalian target rapamycin kinase, can be inhibited by rapamycin. We report that, despite...
Background Immunotherapies are becoming front-line treatments for many advanced cancers, and combinations of two or more therapies beginning to be investigated. Based on their individual antitumor capabilities, we sought determine whether combination oncolytic virus (OV) radiation therapy (RT) may improve cancer outcomes. Methods To investigate the activity this therapy, used in vitro mouse human cell lines as well a model skin cancer. After initial results, further included immune...
Abstract Memory CD8 T cells, essential for defense against intracellular pathogens, are heterogeneous with respect to phenotype and function. Constitutively lytic effector memory cells primarily reside in nonlymphoid tissues, whereas secondary lymphoid tissues contain functionally quiescent central cells. However, the mechanism by which distinct populations maintained is unknown. In this study, we show that resting modified their functional abilities upon entry into as exemplified induction...
Transforming growth factor-beta (TGF-β) is produced by a number of tumor cell types including human malignant mesothelioma (MM), but its role as direct or indirect factor in tumorigenesis incompletely understood. We have investigated the expression TGF-β isoforms and murine MM cells analysed effects inducible antisense RNA-mediated inhibition on vitro vivo. The results showed that (a) -β2 were both mouse cells, (b) RNA against either TGF-β1 cross-inhibited β2 expression, (c) reduced...
Abstract Expression of IL-7Rα on a subset Ag-specific effector CD8 T cells is believed to identify memory cell precursors. However, whether IL-7 regulates expression in vivo and responsible for selective survival IL-7Rα+ unknown. Our results show that the absence IL-7, was extinguished majority responding virus infection, sustained transitioning memory, expressed at high levels by cells. Additionally, an IL-7-deficient environment capable supporting bcl-2 up-regulation development response...
Abstract IL-15 is an essential cytokine known to promote T cell survival and activate the effector function of memory phenotype CD8 cells. Blocking signals also significantly impacts tissue-specific formation. In this study, we demonstrate that influences generation cells by first promoting their accumulation into mucosal tissues second sustaining expression Bcl-6 T-bet. We show mechanism for recruitment largely dependent on mammalian target rapamycin its subsequent inactivation FoxO1. Last,...
Abstract Whether memory CD8 T cells can be reactivated in nonlymphoid tissues is unclear. Using mice lacking the spleen, lymph nodes, or both, we show that secondary cell response, but not homeostatic maintenance of cells, required lymphoid tissue. Whereas primary and responses to vesicular stomatitis virus infection were node dependent, Listeria monocytogenes driven primarily spleen. Memory subset reactivation was also regulated by location responding population pathogen. Thus, CD62Llow...
Abstract Ag-specific Th1 and Th2 cytokine-producing CD4 T cells were quantitated in secondary lymphoid tertiary tissues following oral Listeria monocytogenes infection. Although the response to was previously believed be predominately like, producing IL-4 or IL-5 comprised a substantial proportion of overall primary memory response. The frequency IFN-γ-, IL-4-, IL-5-producing effector significantly higher lung, liver, intestinal lamina propria (LP) as compared with spleen lymph node....