The Journal of Immunology, Vol 156, Issue 12 4631-4637, Copyright © 1996 by American Association of Immunologists

ARTICLES

CD95 engagement releases calcium from intracellular stores of long term activated, apoptosis-prone gammadelta T cells

P Rovere, E Clementi, M Ferrarini, S Heltai, C Sciorati, MG Sabbadini, C Rugarli and AA Manfredi
Second Department of Medicine, Laboratory of Immunology and Receptor Biochemistry Unit, University of Milan School of Medicine, Milan, Italy.

Engagement of the CD95 (Apo-1, Fas) membrane receptor is known to induce apoptosis in a variety of sensitive cells, even in the absence of extracellular Ca2+. The signal transduction events implicated in this pathway are poorly understood. We have recently characterized normal human Vgamma9/Vdelta2+ T cell clones that maintain similar levels of CD95 membrane expression throughout the culture. Here we show that 3 wk of culture after in vitro restimulation are necessary for the cells both to die and to acquire the ability to mobilize intracellular Ca2+ upon CD95 ligation. Buffering of intracellular Ca2+ by accumulation of the chelator 1,2-bis(2-amino phenoxy)ethane-N,N,N1,N- tetraacetic acid protects from CD95-triggered apoptosis, suggesting that the two phenomena are causally related. As intracellular Ca2+ release by inhibition of endoplasmic reticulum ATPases induces apoptosis in both recently and long term activated gamma delta cells, the molecular regulation of activation-dependent apoptosis is likely to involve events upstream of CD95-dependent Ca2+ release. The CD95- triggered increase in the intracellular Ca2+ concentration depends on depletion of the same intracellular Ca2+ stores mobilized by ligation of the TCR, and Ca2+ release does not depend on inositol 1,4,5- trisphosphate generation.

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