Visualizing the Viral Burden: Phenotypic and Functional Alterations of T Cells and APCs during Persistent Infection

Dirk Homann, Dorian B. McGavern, Michael B.A. Oldstone

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

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.

Original languageEnglish
Pages (from-to)6239-6250
Number of pages12
JournalJournal of Immunology
Volume172
Issue number10
DOIs
StatePublished - 15 May 2004
Externally publishedYes

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