The selective growth of murine newborn-derived suppressor cells and their probable mode of action

Naturally occurring suppressor cells residing in the spleens of newborn mice of less than 5 days old are known to suppress various lymphocyte activities. A population of these suppressor cells can be maintained and expanded in the supernatants derived from Wehi-3 cells. These suppressor cells, designated as Wehi-3-expanded neonatal splenocytes (WENS), can suppress mixed lymphocyte reactions (MLR) and T and B cell mitogen responses without any genetic restrictions. The WENS bear the Ly-5, J11d, and class I molecules. WENS suppression is not mediated through an interleukin 1 or interleukin 2 absorptive mechanism. To achieve maximum suppression of MLR, WENS must be present for at least 24 hr. WENS inhibited the proliferation of Wehi-164 cells but not other tumor cells. The inhibition of Wehi-164 growth was due to the action of natural cytotoxic cells, because WENS lysed Wehi-164 cells but not the natural killer target cell YAC-1. Maximum lysis of Wehi-164 by WENS required 18 to 24 hr. Five WENS cell lines were cultured for more than 6 mo; three of the cell lines lost their capacity to lyse Wehi-164 targets (natural cytotoxicity) and simultaneously lost their natural suppressor activity. The two WENS lines that retained natural cytotoxicity also retained natural suppressor activity. Thus, natural suppressor cells may manifest their suppression through a natural cytotoxicity mechanism.