Endothelial Cells Enhance the Human Pokeweed Mitogen Lymphocyte Response

Abstract

The effect of endothelial cells (EC) on lymphocyte mitogen responses was examined. Irradiated or mitomycin C treated EC were co-cultured with allogeneic peripheral blood mononuclear cells (PBM), and proliferative responses to pokeweed mitogen (PWM) and phytohemagglutinin (PHA) were assessed by 3H-thymidine incorporation. Compared to lymphocyte responses in the absence of EC, EC co-culture enhanced PWM responses at 72 hours by 55 +/- 28%, 103 +/- 24%, and 96 +/- 9% at EC:PBM ratios of 1:30, 1:10, and 1:3, respectively. The EC co-culture also resulted in significant lymphocyte responses to otherwise submitogenic doses of PWM (10(-4) micrograms/ml) as well as an accelerated kinetics of response. There was no effect of EC on PHA responses. The EC effect appeared not to require cell contact for its expression; however, supernates of EC cultures were not capable of reproducing the effect. On a cell-for-cell basis, EC were more potent in enhancing responses of adherent-cell-depleted lymphocytes than either allogeneic or syngeneic monocytes. Fibroblasts could not substitute for EC in enhancing PWM response, suggesting that the effect was not a nonspecific feeder phenomenon. The EC may play a role in modulating some immune responses in vivo, especially those occurring in areas of inflammation, neovascularization, and endothelial cell proliferation.

Accessory Cell Function of Human Vascular Endothelial Cells in Pokeweed-Mitogen-Stimulated Immunoglobulin Production by Peripheral Blood Lymphocytes

“…On the other hand, Shanahan et al [11] reported that virgin EC but not fibroblasts enhance the human lymphocyte response to PWM. Roska et al [19], utiliz ing guinea pig aortic EC which do not bear la anti gen, demonstrated that EC are capable of functioning as accessory cells for mitogen (phytohemagglutinin and concanavalin A)-induced T cell proliferation but are unable to present an antigen to primed T cells.…”

“…Lymphocytes and monocytes which are major participants in the immune response emigrate into tis sue through EC from blood vessels. It has been shown that human vascular EC were effective accessory cells for the proliferating response of mitogen-stimulated T lymphocytes [10,11] and were capable of presenting antigen to syngeneic T lymphocytes [12][13][14], In addi tion, it has been demonstrated that class II antigen ex pression by EC is inducible in vitro [ 15].…”

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

“…Previous studies have documented the adherence of T cells to EC (1], and the modulation by EC of T-lymphocyte proliferation in response to mitogens [2][3][4], and in mixed lymphocyte cultures [5], EC can also present antigen to T cells [6,7], We recently demonstrated that EC support mitogeninduced interleukin-2 (IL-2) secretion by T cells more efficiently than do equal numbers of mono cytes [8,9].…”