Role of hydrogen peroxide in the cytotoxic reaction of T lymphocytes

Evidence is presented that T lymphocyte cytotoxicity is mediated by hydrogen peroxide (H202). At a concentration of 5 x 10'- M H202 induced 51Cr release from pre-labelled P815 mastocytoma cells. H202 was generated when T lymphocytes from mouse spleen were exposed to P815 cells. The concentration of H202 produced was apparently one thousand times lower than the con-centration required to lyse the P815 cells. This suggests that the H202 is produced and acts at a highly localized site on the target cell. Sulphydryl groups on the target cell were particularly sensitive both to H202 and to spleen cell attack. The activity of the spleen cells was inhibited by cyanide and azide and by reducing agents which protected the target cells. Cytotoxicity was enhanced by agents which prevented H202 breakdown