Co-engagement of CD3 with LFA-1 or ICAM-1 adhesion molecules enhances the frequency of activation of single murine CD4+ and CD8+ T cells and induces synthesis of IL-3 and IFN-gamma but not IL-4 or IL-6.
Interaction between the cell adhesion molecules lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) augments T cell activation by increasing the avidity of T cell/antigen-presenting cell (APC) binding. To examine whether LFA-1 and ICAM-1 can also contribute to T cell activation in the absence of APCs, single murine CD4+ and CD8+ T cells were cultured with IL-2 and immobilized antibodies to CD3, CD4 or CD8, and LFA-1 or ICAM-1. The combination of anti-CD3, anti-CD4/CD8, and IL-2 stimulated approximately 20% of CD4+ cells and 30% of CD8+ cells to proliferate. Inclusion of anti-ICAM-1 antibody increased these frequencies to 30 and 40% respectively. Maximum activation frequencies were obtained with the combination of anti-CD3, anti-CD4/CD8, and anti-LFA-1 which stimulated cell division by approximately 40% of single CD4+ cells and at least 60% of single CD8+ cells. Under these conditions, 30-40% of the resultant CD4+ clones and greater than 90% of CD8+ clones secreted IL-3 and IFN-gamma. In addition to responding at higher frequencies that CD4+ cells, CD8+ cells formed larger clones which produced 4-fold higher levels of both cytokines. Although the expression of IL-2, IL-3, IFN-gamma, granulocyte-macrophage colony stimulating factor and tumor necrosis factor alpha could be detected in CD4+ and CD8+ clones at the mRNA level following reverse transcription and polymerase chain reaction amplification, neither the secreted nor mRNA expression of IL-4 or IL-6 was detected in any of the tested clones. It is concluded that co-stimulation of T cells via LFA-1 or ICAM-1 can enhance T cell receptor-dependent activation in the absence of accessory cells and that this mode of stimulation leads to the expression of a restricted range of cytokine genes.
Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, Victoria, Australia.
E
E
Maraskovsky
A B
AB
Troutt
A
A
Kelso
D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004247:DNA / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016207:Cytokines; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D004247:DNA