Depressive effect of silica particles on F1 hybrid anti-parent cell-mediated lympholysis induced in vitro

The role of macrophage-like cells in the in vitro generation of specific B6D2F 1 hybrid anti-parental B6 cytotoxic T lymphocytes (CTL) was investigated by means of silica particles (SIL). Depression of this cell-mediated response resulted from the addition of 12.5 or 25 μg of SIL to mixed F 1 /parent spleen cell cultuers, and full abrogation resulted from the addition of 125 or 250 μg of SIL. The treatment was effective if applied during the first 48 hr of culture. When treatment was delayed, responsiveness did not decline nor did the lytic function of mature CTL exposed to SIL. Moreover, no depression of the anti-allogeneic cell mediated response resulted from the addition of 250 or 500 μg of SIL to mixed F 1 /allogeneic instead of F 1 /parent spleen cell cultures. Abrogation of the F 1 hybrid anti-parent response was attributed to SIL-induced impairment of an accessory function presumably exerted by macrophage-like cells during the early phases of responder T cell activation. If so, the F 1 anti-parent response was considerably more dependent than the allogeneic response on the integrity of accessory cells. Injection of 5 mg of SIL to donors of responder cells likewise resulted in loss of F 1 anti-parent and occasionally of anti-allogeneic in vitro responsiveness. This in vivo effect of SIL was prevented by pretreating mice with the lysosomal stabilizer poly-2-vinylpyridine N -oxide. Because unresponsiveness induced in vivo was not selective for F 1 anti-parent responses and lasted for up to 10 days, it may be attributable not only to depletion of accessory macrophages by SIL but also to the induction of suppressor macrophages.