Specific and nonspecific immunoregulatory events in the clonal response of human lymphocytes in vitro.

Stimulation of sensitive leucocyte populations with near optimal concentrations of soluble microbial antigens results in vigorous lymphocyte proliferation when 3H-thymidine incorporation is measured after 4–8 days. Lymphoblasts in these cultures revert to small lymphocytes after 10–14 days, at which time they are often refractory to any stimulant including the original incubating antigen. When these primed lymphocytes are irradiated with 500–1000 R to block their proliferation and added to fresh leucocyte culture from the same individual (autologous), they usually, but not invariably, reduce the proliferation of the unirradiated fresh leucocyte cultures. Exposure to 6000 R reduced the suppressor activity. Reduction was specific for the microbial antigen with which they were originally generated, but, more often, a combination of both specific and nonspecific suppression was observed. These data provide good evidence, with reciprocal specificity, for the generation of antigen specific suppression in vitro.