Ligation of leukocyte function-associated (LFA) molecule-1 provides an accessory signal for T-cell activation with pokeweed mitogen.
The ligation between leucocyte-Function-Associated Molecule 1 (LFA-1) and Intercellular Adhesion Molecules (ICAM) is thought to be an important component in the stimulatory interaction between antigen-presenting cells (APC) and T cells. Similar to antigenic stimulation, T-cell stimulation with pokeweed mitogen (PWM) is highly dependent on monocytes as accessory cells. This is partly a consequence of the requirement for mitogen presentation by the monocytes. The study described here addressed the question of whether LFA-1 ligation by accessory cells influences the activation of T cells with PWM. To avoid multiple costimulatory interactions between T cells and monocytes, experiments were performed with purified T cells, which were stimulated with PWM bound on autologous red blood cells (PWM-RBC). Binding on the RBC substituted partly for PWM presentation by the monocytes. Anti-LFA-1 MoAbs were presented in the immobilized form in order to mimick LFA-1 ligation by cell-bound ICAM. Three out of three different MoAbs against the beta-chain of the LFA-1 molecule (CD18) and two out of three MoAbs against the alpha-chain (CD11a) had an enhancing effect on T-cell proliferation. Proliferation was increased further by simultaneous addition of interleukin (IL)-1 beta and IL-6. Ligation of the LFA-1 molecule was found to enhance IL-2 production and tumour necrosis factor-alpha (TNF-alpha) production. The results suggest that interaction of LFA-1 with ICAM on the monocytes contributes to the accessory signal activity of monocytes in T-cell activation with PWM.