The effect of the polyclonal T-cell activators (PTA) Con A and PHA on the specific immune response to sheep red blood cells (SRC) was studied. Addition of PTA either enhanced or suppressed the anti-SRC response, and two variables were found to affect the results: time of addition of the PTA and the strength of the response in control cultures not given PTA. If the response was high, even suboptimal PTA concentrations induced suppressive effects, but if the control response was low, due to deficient batches of sera or because of the absence of serum, the addition of PTA increased the response or restored it to normal levels. Suppression could be obtained if the PTA were added before or at the same time as the antigen and required high (optimal) PTA concentrations. If addition was delayed for 12-24 h the suppressive effects disappeared and previously suppressive concentrations of the PTA now caused an enhanced response. Analogous results were obtained if preactivated lymphocytes were added to the cultures instead of soluble PTA. Neither Con A, PHA, or lymphocytes preactivated by these PTA suppressed the polyclonal response induced by LPS or PPD. Irrespective of the time of addition and the culture conditions, enhancement of the anti-SRC response occurred at lower PTA concentrations than suppression. It was concluded that suppressor T cells, if they exist, do not act on B cells, but rather on helper cells needed for induction of thymus-dependent responses. The findings in this system are not compatible with the existence of a specific subset of suppressor T cells, but rather with the notion that suppression is caused by too much help.

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