Non-specific inhibitory processes of immunological and mitogenic cellular responses

The suppressive effects of four agents on several types of in vitro immune response and on in vitro responses to T and B mitogens were studied comparatively in spleen cells from C57B1/6 mice, previously injected with each of these agents. It was found that the in vitro PFC response to sheep erythrocytes was the most constantly and extensively inhibited: from 56% after treatment with Con A to 85% after treatment with HSA; LPS and C. parvum also provoked a strong inhibition (74-78%). Inhibition of MLC was constant but less effective, ranging from 36% (LPS) to 57% (C. parvum); HSA and Con A depressed it by about 50%. The CML reaction was substantially inhibited by C. parvum (50%), moderately by Con A and LPS (respectively, 23 and 28%) and slightly by HSA (15%). The inhibition of mitogenic response to PHA and LPS varied widely with the agent used: the PHA response was strongly inhibited by Con A (84%) to a lesser extent by C. parvum (54%) and even less by LPS (27%), whereas HSA did not affect it. LPS reactivity was well inhibited by C. parvum (57%), moderately by Con A (25%), slightly by HSA and not at all by LPS. Most of these agents produced a slight but significant prolongation of skin graft survival time. In vitro experiments using mixtures of spleen cells from treated and normal animals showed that these inhibitory effects were mediated by suppressive cells that developed as a result of the treatment used. The degree of inhibition observed in the mixed cultures satisfactorily paralleled the direct inhibition observed in cells from treated animals. The more consistently suppressive agents seemed to be C. parvum and Con A, the effects of the other two (HSA and LPS) on the cellular responses studied were less regular.