Cell Interactions that Regulate the T-Cell Dose-Response Profile to Concanavalin A

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Abstract
We have tested the ability of structures on macrophage (Mφ) membranes (Mφ-MEM) and on several other types of cells with Fc receptors to affect the DNA synthetic response of concanavalin-A-stimulated T cells. Of the cells tested, only Mφ-MEM have the capacity to relieve the suppression produced by supra-optimal doses of the mitogen. The Mφ-MEM do not increase Con A responses by altering the stimulated capacity of the Con A. These observations, analysed together with previous results, which have indicated that live intact Mφ are required for the transfer of information between lymphocyte sets and that Mφ-MEM preparations can act as competitive antagonists for this function, are interpreted as follows: some supraoptimal doses of Con A activate suppressor cells, which are responsible for limiting the DNA synthetic response to the mitogen; the Mφ-MEM abrogate this suppression by absorbing the signal that activates the suppressor cell. Kinetic studies suggest that the Mφ-MEM do not affect the activity of already activated suppressor cells. We also found that Con A usually activates two separately responding T-cell populations with different sensitivities to dose and to time of contact with mitogen and that the suppression of both populations can be relieved by Mφ-MEM. These results support the notion that the overall immunological circuit is composed of multiple independently regulated mini-circuits, with Mφ acting as transmission posts for intra- and perhaps also inter-circuit communication.