A SUSTAINED INCREASE OF CYTOSOLIC CA2-DELTA T-CELLS TRIGGERED BY CO-STIMULATION VIA TCR( IN GAMMA)CD3 AND LFA-1/

We previously reported that co-stimulation with LFA-1 triggered apopto sis in gamma delta T cells but not in alpha beta T cells after TCR eng agement, We extended our earlier study on TCR/LFA-1 triggered apoptosi s to two autoreactive TCR gamma delta and TCR alpha beta T cell clones , which were derived from syngenic mixed lymphocyte culture of BALB/c mice. A gamma delta T cell clone, KM1, expressed the V gamma 4 and V d elta 5 genes and CD4(-)CD8(-)CD45RB(+) phenotype; and an alpha beta T cell clone, BASL1.1, expressed V beta 6 and CD4(+)CD8(-)CD45RB(+). Bot h clones produced Th-1-type cytokines in response to syngeneic BALB/c stimulator cells. KM1 underwent apoptosis upon stimulation with immobi lized anti-CD3/LFA-1 mAbs, whereas BASL1.1 could proliferate successfu lly in response to stimulation with the immobilized mAbs. BASL1.1 was able to downregulate the increased cytosolic Ca2+ after the simultaneo us stimulation, but KM1 exhibited a sustained increase of cytosolic Ca 2+ after stimulation via CD3 and LFA-1. Similar results with respect t o the kinetics of cytosolic Ca2+ were obtained with normal heterogeneo us gamma delta and alpha beta T cell populations after co-stimulation via CD3 and LFA-1. Our results suggested that persistently high levels of cytosolic Ca2+ might be related to apoptosis in gamma delta T cell clone triggered by costimulation via CD3 and LFA-1.