Regulation of lymphocyte reactivity by plasma fibronectin: cellular requirements

Purified rat plasma fibronectin (Fn) induces significant inhibition of rat lymph node T cell reactivity to PHA in the presence of enriched populations of macrophage accessory cells. The pattern of inhibition is similar whether macrophages are obtained from peritoneal exudates or spleen. Maximal inhibition by Fn is effected at macrophage concentrations higher (2-3% of the T cell number) than that required for optimal lymphocyte proliferation (0.5-1.0%), however significant inhibition was also demonstrated at these optimal concentrations. Fn-pulsed adherent macrophages, when used as accessory cells, are capable of inducing significant inhibition of T cell reactivity to PHA although to a lesser degree than when Fn is continuously present throughout the culture period. Pulsing purified T cells with Fn has no effect on the proliferative response. Nondialyzed supernatants from 24 hour cocultures of peritoneal exudate macrophages and Fn fail to influence the T cell proliferative response when compared to supernatants from macrophages cultured in medium only or with added rat serum albumin. Thus, the inhibitory effect evoked by Fn appears to be mediated at the accessory cell membrane and not by the enhanced production of soluble inhibitors released as a result of the Fn-macrophage interaction.