Brief Definitive Report Lymphocyte Dysfunction after Dna Damage by Toxic Oxygen Species a Model of Immunodeficiency

Immune attri t ion may occur in association with severe chronic infections and neoplastic diseases (1). Mechanisms o f immunodeficiency in these disorders have not been elucidated precisely. During inf lammatory states, activated neutrophils release toxic oxygen species into the extracellular envi ronment (2). T h e oxygen products can damage the DNA of adjacent cells (3). T h e accumulation of DNA strand breaks markedly stimulates the activity of the chromat in-bound enzyme poly(ADP-ribose) synthetase (4). T h e addition o f poly(ADP-ribose) to nuclear proteins has been repor ted (5) to facilitate DNA ligation. However , the rapid synthesis of the ADP-ribose polymer can also deplete cellular pools of NAD + (6). Recently (7), the unrest ra ined synthesis of poly(ADP-ribose) in iymphocytes with unrepai red DNA strand breaks has been postulated to be a possible cause of immune deficiency in children who lack adenosine deaminase. Herein, we document the central role of DNA strand breakage and the p ro g ram m ed synthesis o f poly(ADP-ribose) in the genesis o f lymphocyte dysfunction induced by exposure o f normal resting human PBL to toxic oxygen species.