ICAM-3 (CD50) cross-linking augments signaling in CD3-activated peripheralhuman T lymphocytes

ICAM-3 is a pan-hematopoietic, constitutive adhesion molecule. ICAM-3 binds to LFA-1 on antigen-presenting cells (APC) stabilizing the T cell-APC inte raction, facilitating signaling through the CD3/TCR complex. However, recen t evidence using cultured and transformed T cells suggests ICAM-3 may also function in signaling. Because ICAIM-3 is constitutively expressed on resti ng T cells, we postulated that signaling through ICAM-3 in resting T cells represents an important costimulatory mechanism in these cells, In purified resting human T cells, cross-linking both ICAM-3 and CD3 with plate-bound antibodies resulted in a marked increase in cell size (consistent with blas togenesis), synergistically increased surface expression of CD25 and CD69, and increased T cell metabolism. Similarly, concomitant ICAM-3 and CD3 stim ulation significantly (P < 0.001) increased resting human T cell phosphatid ylinositol hydrolysis and phospholipase C-gamma 1 phosphorylation, These re sults indicate that ICAM-3 augments signaling through CD3, functioning as a costimulatory molecule for resting T cells in the initial activation step.