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The purpose of this study was to examine the role of IL-2 and helper T-lymphocytes in the development of periradicular lesions in rats. In control animals, periradicular lesions developed within 28 days following pulpal infection. Immunologically, some anti IL-2 and anti CD4-reactive helper T-lymphocytes infiltrated the periapical tissue at 14 days, and their numbers increased at 28 days. In experimental animals, tacrolimus (FK506) was injected every day to inhibit the IL-2 production by helper T-cells. Histologically, the pulpal necrosis and periradicular inflammation in tacrolimus-treated rats were more severe than those in the control rats. Furthermore, the areas of pulpal necrosis and periradicular lesion in the immunosuppressed rat were significantly greater than those in the normal ones. The numbers of IL-2- and CD4-positive cells in the lesion of the experimental rats were statistically lower than those of the control ones. These results show that the decrease in IL-2 might have promoted the development of periradicular lesions.