Effect of 1-thiocarbamoyl-2-imidazolidinone on the generation of plaque forming cell responses.

Abstract

Although 1-thiocarbamoyl-2-imidazolidinone (TCI) is a highly potent modulator of cellular immunity, its effects on humoral immunity have not been investigated. Given orally to mice prior to immunization with sheep red blood cells (SRBC), low TCI doses (10(-14) to 10(-10) g/kg) suppressed primary plaque forming cell (PFC) responses of spleen cells by 50-75%. TCI effects in vivo were dependent on drug dose, antigen dose and time of drug administration relative to immunization. The kinetics of this response were not appreciably altered by TCI. Higher TCI doses, immunization with higher levels of SRBC than required to produce a maximal response or administration of TCI later than 48 hours after immunization resulted in drug effects ranging from slight suppression to mild enhancement of the primary PFC response. TCI given in vivo enhanced primary PFC responses to the T-independent antigen DNP-Ficoll by greater than 700%+. TCI given before a primary immunization suppressed a secondary PFC response to SRBC elicited 28 days later. However, when TCI was given 24 h prior to a secondary immunization, doses greater than 10(-5) g/kg were necessary to suppress the PFC response. The effect of TCI on in vitro immunized spleen cell cultures was similar to that found for in vivo immunized mice. TCI at concentrations up to 10(-1) g/l did not cause a loss of lymphocyte viability or inhibit plaque production by antibody producing cells. Effects of TCI on PFC responses in vitro were reversible if cells briefly exposed to an optimal concentration of drug were washed extensively prior to immunization.(ABSTRACT TRUNCATED AT 250 WORDS)