CHARACTERIZATION OF VIRUS-PRIMED CD8(-CELLS WITH A TYPE-1 CYTOKINE PROFILE() T)

Infection with lymphocytic choriomeningitis virus is associated with m arked polyclonal activation of the CD8(+) T cell subpopulation. In thi s report the cytokine production of virus-activated T cells is analyze d and the producing cell subset is characterized phenotypically. Coinc iding with other parameters of cell-mediated immunity, splenic T cells appear which are able to release high amounts of IFN-gamma, but not I L-5, IL-10 or tumor necrosis factor-alpha upon short-term stimulation with anti-CD3 in vitro. A similar profile is observed analyzing T cell s taken from an inflammatory site. Phenotypically, the main cytokine-p roducing cell subset is found to be CD8(+) cells targeted for homing t o inflammatory sites (VLA-4(hi)L-selectin(lo)) of which 30-40% were po sitive by intracellular staining for IFN-gamma. This subset also conta ins all T cells with a cytotoxic potential as measured by redirected k illing. An enhanced cytotoxic potential as well as an increased capaci ty to produce IFN-gamma is observed for at least 2 months after infect ion and cell sorting analysis revealed that this could be ascribed to a long-standing increase in the frequency of CD8(+)Pgp-1(hi) cells. Th erefore, these results demonstrate that systemic virus infection may e xert marked perturbation of the CD8(+) T cell population resulting in generation of a long-lived subset of primed cells with important effec tor potential.