Department of Pathology
Animals; Calcium Chloride; Cytoplasmic Granules; *Cytotoxicity, Immunologic; DNA; Egtazic Acid; Esterases; Hemolysis; Leukocytes; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Magnesium Chloride; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Spleen; T-Lymphocytes, Cytotoxic
Life Sciences | Medicine and Health Sciences
The mechanism of lysis by in vivo-induced cytotoxic T lymphocytes (CTL) was examined with virus-specific CTL from mice infected with lymphocytic choriomeningitis virus (LCMV). LCMV-induced T cells were shown to have greater than 10 times the serine esterase activity of T cells from normal mice, and high levels of serine esterase were located in the LCMV-induced CD8+ cell population. Serine esterase was also induced in purified T-cell preparations isolated from mice infected with other viruses (mouse hepatitis, Pichinde, and vaccinia). In contrast, the interferon inducer poly(I.C) only marginally enhanced serine esterase in T cells. Serine esterase activity was released from the LCMV-induced T cells upon incubation with syngeneic but not allogeneic LCMV-infected target cells. Both cytotoxicity and the release of serine esterase were calcium dependent. Serine esterase released from disrupted LCMV-induced T cells was in the form of the fast-sedimenting particles, suggesting its inclusion in granules. Competitive substrates for serine esterase blocked killing by LCMV-specific CTL, but serine esterase-containing granules isolated from LCMV-induced CTL, in contrast to granules isolated from a rat natural killer cell tumor line, did not display detectable hemolytic activity. Fragmentation of target cell DNA was observed during the lytic process mediated by LCMV-specific CTL, and the release of the DNA label [125I]iododeoxyuridine from target cells and the accompanying fragmentation of DNA also were calcium dependent. These data support the hypothesis that the mechanism of killing by in vivo-induced T cells involves a calcium-dependent secretion of serine esterase-containing granules and a target cell death by a process involving nuclear degradation and DNA fragmentation.
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Citation: J Virol. 1990 Aug;64(8):3726-33.
Journal of virology
Welsh, Raymond M.; Nishioka, Walter K.; Antia, Rustom; and Dundon, Patricia L., "Mechanism of killing by virus-induced cytotoxic T lymphocytes elicited in vivo" (1990). Open Access Articles. 1577.