High numbers of mononuclear leukocytes (MNL) in one compartment of a diffusion chamber profoundly suppressed lymphocyte responses in the other compartment. Suppression was expressed by decreased incorporation of labeled thymidine, uridine, and leucine and lowered blastogenesis in T-lymphoproliferative cultures as well as reduced Ig synthesis. The inhibitory effect, which was reversible, was experienced predominantly during the later stages of the culture period. Suppression of both autologous and allogeneic effector cells was associated with a radioresistant, moderately adherent non-T-cell subpopulation that did not require activation. Cell contact was not required suggesting that suppression was related to release of a mediator. This mediator was of low molecular weight and was remarkably labile. Only a portion of this modulation could be ascribed to prostaglandins and none to products of the lipoxygenase pathway, hydrogen peroxide, or the accumulation of thymidine.
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