Characterization of virus-primed CD8+ T cells with a type 1 cytokine profile.
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.
Christensen
J P
JP
Institute of Medical Microbiology and Immunology, Panum Institute, Copenhagen, Denmark.
Stenvang
J P
JP
Marker
O
O
Thomsen
A R
AR
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D006918:Hydroxyurea / Q000494:pharmacology; D007249:Inflammation; D039041:Integrin alpha4beta1; D016023:Integrins / Q000032:analysis; D007371:Interferon-gamma / Q000032:analysis*; D016753:Interleukin-10 / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D019041:L-Selectin / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D039041:Integrin alpha4beta1; D016023:Integrins; D015848:Interleukin-5; D016201:Receptors, Lymphocyte Homing; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D016753:Interleukin-10; D007371:Interferon-gamma; D006918:Hydroxyurea