In Jurkat T cells, the type 3 ryanodine receptor (RyR) was knocked-down by stable integration of plasmid expressing type 3 ryanodine receptor antisense RNA.
Ca 2ϩ signaling by ligation of the T cell receptor (TCR)/CD31 complex is a complicated process involving the formation and breakdown of the second messengers D-myo-inositol 1,4,5-trisphosphate (IP 3 ) and cyclic adenosine diphosphoribose (cADPR) in a temporally coordinated fashion (1-3). In addition to IP 3 and cADPR, nicotinic acid adenine dinucleotide phosphate (NAADP) is an essential regulator of T cell Ca 2ϩ signaling (4), although the exact role of this nucleotide has not yet been clarified. Jurkat T cells preincubated with the specific, membrane-permeant cADPR antagonist 7-deaza-8-Br-cADPR (5) showed characteristic defects in the onset and in the longlasting phase of TCR/CD3-and  1 -integrin-mediated Ca 2ϩ signaling (2, 6). In addition, in peripheral human T cells, 7-deaza-8-Br-cADPR efficiently blocked expression of the activation antigens CD25 and MHCII and blocked proliferation upon CD3