Increased DNA synthesis in vitro in guinea-pigs unresponsive to DNP--skin protein conjugate.

Immunological unresponsiveness to DNP—guinea-pig skin protein conjugate (DNP—GPSP) was induced by intravenous injections of dinitrobenzene-sulphonic acid (DNBSO) given before, simultaneously, or after sensitization with DNP—GPSP. The increased DNA synthesis by lymph node or peritoneal exudate lymphocytes from unresponsive guinea-pigs was suppressed only in animals tolerized by pretreatment with DNBSO. The majority of guinea-pigs with the other two types of unresponsiveness showed an increased [H]thymidine incorporation into lymph node—but not into peritoneal exudate lymphocytes. From these results two conclusions may be drawn: (1) the mechanism of unresponsiveness induced during the primary response is similar to that of desensitization and different from that of `classical' tolerance; (2) tolerogen given before the sensitization prevents both the increased DNA synthesis by lymph node and peritoneal exudate lymphocytes and the skin reaction. Tolerogen given during the primary response or after the sensitization prevents increased DNA synthesis by peripheral lymphoid cells (peritoneal exudate lymphocytes) and the skin reaction, whereas lymph node lymphocytes showed increased DNA synthesis.