CD2 (OKT11) augments CD3-mediated intracellular signaling events in human T lymphocytes

CD2 (LFA-2) is expressed on thymocytes, natural killer cells, and virtually all peripheral T cells, CD2 binds to its primary ligand CD58 (LFA-3) on an tigen presenting cells (APC) and stabilizes the T cell-APC interaction; thi s stable interaction then optimizes Ag-specific T-cell activation. We asses sed whether CD2-cross-linking by mAb augments the process of T-cell stimula tion through the TCR/CD3 complex. Plate-bound anti-CD2 or anti-CD3 mAb alon e had no measurable effect on any of the assessed activation parameters of resting T cells, However, concomitant signaling through both CD2 and CD3 by plate-hound antibodies resulted in marked increases in CD69 expression on the T-cell surface and T-cell-cellular metabolism, as assessed by the abili ty of the cell to reduce 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxylmethoxyp henyl)-2-(4-sulphophenyl)-2H-tetrazolium (MTS) to formazen, In addition, si multaneous cross-linking of CD2 and CD3 caused a significant (P<0.001) incr ease in phosphatidylinositol hydrolysis in resting T cells compared to stim ulation with anti-CD3 mAb alone and anti-CD3 mAb plus anti-CD2 isotype cont rol antibody. These results indicate that CD2 augments signaling through CD 3, and consequently functions as a costimulatory molecule for resting T cel ls in the initial activation step.