Suppression of the generation of secondary virus-specific proliferative and cytotoxic T lymphocytes by suppressor cells induced during primary anti-viral sensitization in vitro.

Murine spleen cells first primed with syngeneic vaccinia virus-infected peritoneal exudate cells (PEC) in vitro and then restimulated with the virus failed to give a typical virus-specific secondary cytotoxic T lymphocyte (CTL) response. In contrast, "memory' spleen cells from mice primed with the virus in vivo produced CTL after the same challenge with virus-infected PEC in vitro. In the former situation, the lack of a virus-specific secondary CTL response by in vitro primed and restimulated spleen cells seemed to be associated with the generation of suppressor cells in cultures; these cells inhibited the cytotoxic as well as proliferative secondary and tertiary responses of spleen presensitized with virus in vitro alone, or in vivo plus in vitro. Weak suppressor activity was also induced in control spleen-cell cultures from normal unprimed or virus-primed mice that were not stimulated with virus-infected cells, suggesting either a quantitative difference in the generation of suppression or, alternatively, the co-existence of virus-dependent and independent suppressor cells in the virus-stimulated cultures. Our experiments cannot conclusively establish that suppression is T-cell mediated and/or possibly natural-killer-(NK)-cell dependent. The suppressor phenomena were exerted by irradiation resistant (850 rad) lymphocytes that passed through nylon wool columns and were sensitive to treatment with anti-Thy-1 antibody plus C; but the suppressor cells were partially reactive across allogeneic barriers.