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-γ 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-presentlng cell (APC) binding. To examine whether LFA-1 and ICAM-1 can also contribute to T cell activation in the absence of APCs1, single murine CD4+ and CD8+ T cells were cultured with IL-2 and immobilized antibodies to CD3, CD4 or CDS, and LFA-1 or ICAM-1. The combination of anti-CD3, anti-CD4/CD8, and IL-2 stimulated -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 -40% of single CD4+ cells and at least 60% of single CD8 + cells. Under these conditions, 30–40% of the resultant CD4+ clones and >90% of CD8+ clones secreted IL-3 and IFN-γ. 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-γ, granulocyte-macrophage colony stimulating factor and tumor necrosis factor α 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.