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A Technique to Simultaneously Visualize Virus-Specific CD8+ T Cells and Virus-Infected Cells In situ
Published on: August 13, 2009
Visualizing the viral burden: phenotypic and functional alterations of T cells and APCs during persistent infection
Dirk Homann1, Dorian B McGavern, Michael B A Oldstone
1Department of Neuropharmacology, Division of Virology, The Scripps Research Institute, La Jolla, CA 92037, USA. dirk.homann@uchsc.edu
Abstract:
Persistent viral infections continue to present major public health problems. Failure to achieve virus control confronts the immune system with a chronic viral burden that may involve immune cells themselves and directly compromise the functionality of effector lymphocytes and APCs. In this study we use the lymphocytic choriomeningitis virus system for persistent viral infection of its natural murine host and use analytical techniques for direct ex vivo visualization of virus-infected immune cells. We report that virtually all cells of the immune system can be infected, but the distribution of the viral burden is differentially allocated to lymphocyte and APC subsets of defined phenotypes. Importantly, the profile of immune cell infection found in the blood is broadly representative for the pattern of cellular infection in most organs and is independent of the presence of Abs or complement. By direct comparison of virus-infected and uninfected cell subsets, we demonstrate that lymphocytic choriomeningitis virus-infected T cells show preferential activation, skewed cytokine profiles, and increased apoptosis. In contrast, increased activation of APCs is generalized and independent of the presence of viral Ag. Our data indicate that specific patterns of immune cell infection are associated with distinct forms of immunostimulatory and immunosuppressive alterations that may provide insights into autoimmune processes associated with infectious disease and offer clues for therapeutic interventions aimed at restoration of complete immunity.
Insights
Persistent viral infections impact the immune system, infecting most immune cells. This study reveals specific infection patterns in lymphocytes and antigen-presenting cells (APCs) that alter immune responses, offering therapeutic insights.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Persistent viral infections pose significant public health challenges.
- Chronic viral burden compromises immune cell function, particularly lymphocytes and antigen-presenting cells (APCs).
- Understanding immune cell susceptibility and response is crucial for managing persistent infections.
Purpose of the Study:
- To investigate the distribution and impact of persistent lymphocytic choriomeningitis virus (LCMV) infection on various immune cell subsets in vivo.
- To analyze the functional consequences of viral infection on T cells and APCs.
- To identify patterns of immune cell infection that correlate with altered immune responses.
Main Methods:
- Utilized the lymphocytic choriomeningitis virus (LCMV) model in its natural murine host.
- Employed direct ex vivo visualization techniques to identify and analyze virus-infected immune cells.
- Compared functional parameters (activation, cytokine profiles, apoptosis) between infected and uninfected immune cell subsets.
Main Results:
- LCMV infects a wide range of immune cells, with differential distribution among lymphocyte and APC subsets.
- Immune cell infection patterns in blood reflect those in most organs and are independent of antibodies or complement.
- LCMV-infected T cells exhibit heightened activation, skewed cytokine production, and increased apoptosis.
- APCs show generalized activation, irrespective of viral antigen presence.
Conclusions:
- Specific patterns of immune cell infection during persistent viral infections are linked to distinct immunostimulatory and immunosuppressive effects.
- These findings provide insights into autoimmune processes associated with infections.
- The study suggests potential therapeutic strategies for restoring immune function in persistent viral diseases.
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