Dissociation of the mitogenic and rosette-forming effects of PHA to stimulators of cyclic AMP levels.

The mitogenic and the spontaneous E-rosette stimulating effects of phytohaemagglutinin (PHA) were studied by examining their responses to an elevation of intracellular cAMP induced by pretreatment with aminophylline, adrenaline or PGE1 or by adding exogenous cAMP. Elevation of the intracellular cAMP levels of lymphocytes was found inhibitory to the mitogenic effect of PHA, while leaving the increased early and stable spontaneous rosette formation unaffected. It also failed to depress the PHA-induced slight increase in the proportion of total spontaneous E-rosette-forming lymphocytes. The responses of the two PHA effects under study to the elevation of the cAMP level are thus dissociated, suggesting that the two effects represent two different manifestations of lymphocyte activation, though these manifestations may not be independent of each other. It has been confirmed that PHA produces a shift primarily within the T-cell population toward the active and the stable E-rosette-forming subpopulation, while the increase in the total E-rosette-forming lymphocyte population is but slight. This may possibly involve the activation of the T-derived "null" cells unable to bind sheep red blood cells without PHA treatment.