Suppression of immune responses to sheep erythrocytes by the lymphokine soluble immune response suppressor (SIRS) in vivo

Soluble immune responses 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, 10³ to 10⁴ 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 supression of PFC responses requires the addition of SIRS 4 to 5 days before assay unless SIRS is activated to SIRS(ox) by H₂O₂. Levamisole, an inhibitor of SIRS-mediated supression 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-γ), 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-γ may be largely mediated by SIRS. These findings indicate that SIRS could contribute to the development of suppressed immunity in vivo.