Endothelial Cells Modulate Both T-Cell-Dependent and T-Cell-Independent Plaque-Forming Cell Generation in vitro

Abstract

The effects of live endothelial cells (EC), paraformaldehyde fixed EC, and EC supernatant were measured on pokeweed mitogen (PWM)-induced T-cell-dependent plaque-forming cell (PFC) generation by peripheral blood mononuclear cell (PBM). At low doses (less than or equal to 2 x 10(4) cells/culture) live EC helped PFC generation. At higher doses (greater than or equal to 10 x 10(4) cells/culture) the effect of live EC was always marked suppression (less than 10% of baseline PFC). In contrast both fixed EC and EC supernatant provided help exclusively over a wide dose range. The EC-helper effect enhanced the sensitivity of PBM to suboptimal PWM doses and also accelerated the rate of PFC generation during culture. EC influences on PFC could not be modified by gamma-interferon induction of surface DR which is known to modify EC accessory cell ability. There was also only minimal helper activity of live EC and fixed EC on the PFC generation by Epstein-Barr virus-induced cultures of purified B cells (which had been depleted of both T cells and monocytes). In contrast, suppression (greater than 97%) of PFC in isolated B-cell cultures was found even when EC constituted less than 1% of cultured cells. These results imply EC have the potential of providing multiple regulatory signals which modulate in vitro antibody production. EC-derived mechanisms are independent of their accessory cell function and require interaction with non-B cells for help, but suppression may occur directly at the B-cell level.(ABSTRACT TRUNCATED AT 250 WORDS)