Antigen-induced in vitro inhibition of immune responsiveness

Addition of the dinitrophenyl derivative of the copolymer of d-glutamic acid and d-lysine (DNP-d-GL) or dinitrophenyl bovine γ-globulin (DNP-BGG) to spleen cell cultures specifically inhibited their capacity to produce an anti-DNP plaque-forming cell (PFC) response to the T-independent antigen dinitrophenylated polyacrylamide beads (DNP-PAA) or to the T-dependent antigen TNP-burro erythrocytes. The degree of unresponsiveness was dependent upon the tolerogen concentration and the duration over which the tolerogen was present in the culture. Treatment with rabbit anti-mouse brain antiserum and complement did not alter the induction of unresponsiveness suggesting a state of B-cell tolerance. Culture of spleen cells for 4 days in the absence of antigen led to the appearance of nonspecific suppressor activity which was demonstrable by its effect on the response of fresh spleen cells to antigen. Preculture in the presence of the immunogen DNP-PAA induced both nonspecific and specific suppressor activities. Induction of specific suppressor activity was not prevented by the presence of the tolerogen DNP-D-GL in the culture. The suppressor activity resided in an adherent T-cell population and did not appear to require macrophages for its induction.