Hybrid resistance to EL-4 lymphoma cells. II. Association between loss of hybrid resistance and detection of suppressor cells after treatment of mice with 89Sr.

Abstract

(C57BL/6 X DBA/2)F1 hybrid (B6D2F1) mice resist the growth of parental-strain (B6) EL-4 lymphoma cells inoculated intraperitoneally; that is, B6D2F1 mice survive longer than B6 mice and do not develop ascites. As compared with B6 mice, B6D2F1 mice have higher levels of natural killer (NK) activity against 51Cr-labelled EL-4 cells in their lymphoid organs. B6D2F1 mice treated with 89Sr lose NK activity for certain lymphoma cell targets, e.g. YAC-1, but NK(EL-4) function is usually intact. However, 89Sr-treated mice had lost hybrid resistance to EL-4 cells in vivo, as determined by survival by irradiated or unirradiated EL-4 cells, Corynebacterium parvum, or polyinosinic:polycytidylic acid (pI:pC) in spleens of normal B6D2F1 mice, but NK(EL-4) activity was depressed within 3 days by such treatment in B6D2F1 mice previously injected with 89Sr. Suppressor cells for NK(EL-4) but not for NK(YAC-1) effectors were easily detected in spleens of 89Sr-treated mice "challenged' with C. parvum. Thus, agents capable of stimulating NK cell function in normal mice may lead to suppression of that activity in mice depleted of marrow-dependent cell function by 89Sr. Spleen cells of 89Sr-treated B6D2F1 mice were also unable to generate anti-EL-4 cytotoxic T lymphocytes in a cell-mediated lympholysis system; this defect appeared also to be mediated by suppressor cells. Lymphoid cells depleted by 89Sr-induced marrow aplasia may have two functions in host defences against tumours (especially lymphomas): they may lyse tumour cells directly and they may "down-regulate' suppressor cells capable of inhibiting other "natural' or "induced' immune functions.