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.
Wallays
G
G
Department of Medicine and Pathophysiology, Catholic University of Leuven, Belgium.
Ceuppens
J L
JL
D000328:Adult; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D018821:CD18 Antigens; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011043:Pokeweed Mitogens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D016169:Lymphocyte Function-Associated Antigen-1; D011043:Pokeweed Mitogens; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4