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Mice naturally tolerant to C5 have T cells that suppress the response to this antigen

We examined whether C5‐sufficient mice which are naturally tolerant to this antigen have suppressor T cells to C5 humoral immune response. Two congenic strains of mice B10.D2 (NSN) and B10.D2 (OSN) differing only in the presence or absence of C5 were used. Irradiated (760 rds) sufficient hosts were reconstituted with a nonadherent spleen cell suspension from either sufficient or deficient mice or a mixture of both. Hemolytic C5 levels were assayed. Sufficient spleen cells appeared to prevent the drop of C5 level caused by anti‐C5 antibody made by deficient spleen cells. Spleen cell suspensions from sufficient mice primed with deficient spleen cells exhibited better anti‐C5 activity than normal sufficient spleen cell suspensions. This anti‐C5 activity is abrogated by treatment of the NSN spleen cell suspensions obtained from NSN primed with OSN spleen cells with anti‐Thy‐1.2 antiserum and complement. Suppression of the humoral response to C5 failed to affect the anti‐sheep red blood cell immune response. Suppressor T cells are resistant to low‐dose irradiation, cortisone treatment and adult thymectomy. In contrast, they are sensitive to high doses of irradiation and both high and low doses of cyclophosphamide treatment. Thus, C5 sufficient mice, in contrast to C5‐deficient mice, appear to have antigen‐specific suppressor T cells which downregulate the humoral immune response to C5.