Dengue virus-induced suppressor factor stimulates production of prostaglandin to mediate suppression

The immunosuppression in dengue type 2 virus (DV)-infected mice is mediated through secretion of a soluble suppressor factor (SF) produced by the T lymphocytes of the spleen. Activity of the suppressor cells was abrogated by pretreatment with indomethacin, indicating that suppression is mediated through prostaglandin (PG) or products of the PG synthetase pathway. The present study was undertaken to resolve the relationship between SF and PG. Treatment of mice with indomethacin did not affect production of SF. Therefore, PG is different from SF and the presence of PG is not essential for its production. Normal mouse spleen cells treated in vitro with SF produced PG which mediated suppression. Production of PG by these cells was abolished by pretreatment with anti-Thy 1.2 antibody and complement. It is concluded, therefore, that immunosuppression occurs in two phases: in the first step DV stimulates a subpopulation of T lymphocytes to produce SF, and in the second step SF induces a subpopulation of T lymphocytes to produce PG or products of the PG synthetase pathway which finally mediate suppression.