Mechanism of Immunosuppression by a Murine Non-specific Suppressor T Cell Line, SB-1

The mechanism of immunosuppression by a murin non-specific suppressor T cell clone (SB-1), which was established from concanavalin A (Con A)-activated murine spleen cells[Jpn. J. Exp. Med., 53, 139 (1983)], was investigated. SB-1-induced decrease of antigen non-specific plaque-forming cell (PFC) response was restored by the addition of 5×10-6 M indomethacin, an inhibitor cyclooxygenase. On the other hand, suppressive activity for antigen non-specific PFC response was found in the culture supernatant of SB-1 cells in the presence of proteose peptone-elicited macrophages. This induction of the suppressive activity was also inhibited by 5×10-6 M indomethacin. Furthermore, 10-5 M prostaglandine E2 (PGE2) was found to induce suppressive activity in the culture supernatant of SB-1 cells. 10-5 M PGE2 did not suppress interleukin-2 (IL-2)-dependent proliferation of SB-1 cells, but increased a small quantity of protein synthesis and deoxyribonucleic acid (DNA) synthesis of SB-1 cells in the absence of IL-2. These results suggest that a cyclooxygenase product(s) such as PGE2 from macrophages may induce production of soluble suppressor factors in SB-1 cells.To characterize these suppressor factors, those in the culture supernatant of PGE2-stimulated SB-1 cells were partially purified by ammonium sulfate fractionation and sequential column chromatographies on diethylaminoethyl (DEAE)-cellulofine and Sephacryl S-200. Suppressor activities were eluted at the positions corresponding to the molecular masses of 10, 30, 70 and over 70 kilodalton (kDa) on Sephacryl S-200 column chromatography. Quite interestingly, the suppressive effects of 10 and 30 kDa factors on non-specific PFC response were reversed by 1 mM N-acetyl-galactosamine but not by equimolar concentration of D-glucose, α-methyl-D-mannoside and L-rhamnose. It seemed that these factors had sugar binding activity like lectins.