Suppression of immune responses to sheep erythrocytes by the lymphokine soluble immune response suppressor (SIRS) in vivo.
Soluble immune response suppressor (SIRS) is a protein produced by activated suppressor T lymphocytes which inhibits division by tumor cells and plaque-forming cell (PFC) responses in vitro. Although this lymphokine has been fairly well characterized in vitro, little is known about its effects in vivo. Purified murine SIRS, 10(3) to 10(4) U injected i.p., suppressed murine PFC responses to sheep erythrocytes (SRBC) in vivo. Suppression occurred when SIRS was injected into mice 5 days before assay, and also occurred when SIRS activated with 10(-6) M H2O2 was injected 24 hr before assay. These kinetics are similar to those observed in tissue culture, where suppression of PFC responses requires the addition of SIRS 4 to 5 days before assay unless SIRS is activated to SIRSox by H2O2. Levamisole, an inhibitor of SIRS-mediated suppression in vitro, also blocked suppression by SIRS in vivo. Delayed-type hypersensitivity reaction to footpad injection of SRBC was also inhibited by SIRS. Suppression of PFC responses by recombinant immune interferon (IFN-gamma), which activates lymphocytes to produce SIRS in vitro, was blocked by injection of levamisole or monoclonal anti-SIRS antibodies. These results show that SIRS suppresses immune responses in vivo, and suggest that suppression of PFC responses by IFN-gamma may be largely mediated by SIRS. These findings indicate that SIRS could contribute to the development of suppressed immunity in vivo.
D000818:Animals; D000917:Antibody Formation; D017707:Erythrocyte Transfusion; D006462:Hemolytic Plaque Technique; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D007978:Levamisole / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012756:Sheep; D013491:Suppressor Factors, Immunologic / Q000008:administration & dosage*
D013491:Suppressor Factors, Immunologic; C013256:soluble immune response suppressor; D007978:Levamisole; D007371:Interferon-gamma