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Characterization of virus-primed CD8+ T cells with a type 1 cytokine profile
J P Christensen1, J P Stenvang, O Marker
1Institute of Medical Microbiology and Immunology, Panum Institute, Copenhagen, Denmark.
Insights
Lymphocytic choriomeningitis virus infection activates CD8+ T cells, generating a long-lived subset with enhanced effector functions. These primed cells produce significant interferon-gamma and exhibit increased cytotoxic potential post-infection.
Area of Science:
- Immunology
- Virology
- Cellular Biology
Background:
- Lymphocytic choriomeningitis virus (LCMV) infection induces significant polyclonal activation of CD8+ T cells.
- Understanding the cytokine production and phenotypic characteristics of virus-activated T cells is crucial for comprehending cell-mediated immunity during viral infections.
Purpose of the Study:
- To analyze the cytokine production profile of virus-activated T cells following LCMV infection.
- To phenotypically characterize the specific T cell subsets responsible for cytokine production and effector functions.
Main Methods:
- Analysis of cytokine production (IFN-gamma, IL-5, IL-10, TNF-alpha) from splenic T cells and T cells from inflammatory sites after in vitro anti-CD3 stimulation.
- Phenotypic characterization of cytokine-producing T cells using intracellular staining for IFN-gamma and surface markers (VLA-4, L-selectin).
- Assessment of cytotoxic potential and analysis of long-term changes in CD8+ T cell subsets (Pgp-1hi) post-infection.
Main Results:
- Virus-activated T cells predominantly produced high amounts of interferon-gamma (IFN-gamma), but not IL-5, IL-10, or tumor necrosis factor-alpha.
- The primary IFN-gamma-producing cell subset consisted of CD8+ T cells with an inflammatory homing phenotype (VLA-4hiL-selectinlo).
- A long-standing increase in CD8+ Pgp-1hi cells was observed, correlating with enhanced cytotoxic potential and IFN-gamma production for at least 2 months post-infection.
Conclusions:
- Systemic viral infections significantly perturb the CD8+ T cell population.
- LCMV infection generates a long-lived subset of primed CD8+ T cells with substantial effector functions, including IFN-gamma production and cytotoxicity.
Abstract:
Infection with lymphocytic choriomeningitis virus is associated with marked polyclonal activation of the CD8+ T cell subpopulation. In this report the cytokine production of virus-activated T cells is analyzed and the producing cell subset is characterized phenotypically. Coinciding with other parameters of cell-mediated immunity, splenic T cells appear which are able to release high amounts of IFN- gamma, but not IL-5, IL-10 or tumor necrosis factor-alpha upon short-term stimulation with anti-CD3 in vitro. A similar profile is observed analyzing T cells taken from an inflammatory site. Phenotypically, the main cytokine-producing cell subset is found to be CD8+ cells targeted for homing to inflammatory sites (VLA-4hiL-selectinlo) of which 30-40% were positive by intracellular staining for IFN-gamma. This subset also contains all T cells with a cytotoxic potential as measured by redirected killing. An enhanced cytotoxic potential as well as an increased capacity to produce IFN-gamma is observed for at least 2 months after infection and cell sorting analysis revealed that this could be ascribed to a long-standing increase in the frequency of CD8+ Pgp-1hi cells. Therefore, these results demonstrate that systemic virus infection may exert marked perturbation of the CD8+ T cell population resulting in generation of a long-lived subset of primed cells with important effector potential.