Suppression of human peripheral blood mononuclear cell response to mitogen by tetanus toxoid. A study of the possible mechanisms.

Abstract

Previous studies have shown that certain antigens can down-regulate immune responses of human peripheral blood mononuclear cells (PBMC) both in vivo and in vitro. This study demonstrates that tetanus toxoid (TT), in a dose-dependent fashion, suppresses the induction of a blastogenic response of PBMC by phytohemagglutinin (PHA), monoclonal anti-CD3, and anti-CD4 antibody. Pokeweed mitogen (PWM)-induction of IgG and IgM is suppressed as well. The suppression is partially reversed by indomethacin and IL-2, but not by IL-1 or tumor necrosis factor (TNF-$\alpha$). PBMC pre-incubated with TT could suppress the PHA blastogenic response of fresh autologous cells during co-incubation. The removal of CD4$\sp+$ cells prior to induction of suppression greatly diminished the suppression of PHA blastogenic response, whereas the elimination of CD8$\sp+$ cells had no effect. Therefore it is concluded that TT induces non-specific suppressor cells that can strongly dampen mitogenic responses, and that CD4$\sp+$ cells plays an important role in this suppression. CD4 $\sp+$ cell, together with monocytes, may suppress mitogenic responses involving a prostaglandin-dependent pathway.