Restoration of T-cell function and induction of antitumor immune response in T-cell-depressed spontaneously hypertensive rats by treatment with thymosin fraction 5.

We studied the effect of treatment with Thymosin Fraction 5 (Fr-5) on the restoration of T-cell functions and the induction of antitumor immunity in spontaneously hypertensive rats (SHR) with congenital T-cell depression. SHR showed a reduced number of rosette-forming thymocytes early in their lives, and in vitro incubation of SHR thymocytes with Fr-5 restored the numbers of rosette-forming T-cells to the normal level for Wistar/HMK rats, the original strain of SHR. In vivo treatment of SHR with various doses of Fr-5 (0.5, 1.0, or 2.0 mg/kg, 6 times every other day) also increased significantly the blastogenic responses of their spleen cells to phytohemagglutinin but failed to promote plaque-forming cell responses to sheep red blood cells. These immunological restorative effects by Fr-5 were dose dependent. In contrast, treatment with lower doses of Fr-5 (0.25 or 0.50 mg/kg) showed greater curative effects on a high antigenic fibrosarcoma (SMT-6) than did treatment with higher doses of Fr-5 (1.0 or 2.0 mg/kg). This was confirmed by the fact that treatment with a 0.5-mg/kg dose of Fr-5 caused a significant suppressive effect on the growth of a weakly antigenic and highly metastatic adenocarcinoma (SST-2) in SHR with a consequent prolongation of survival days, whereas treatment with a 1.0- or 2.0-mg/kg dose of Fr-5 was without any effect. In order to clarify this mechanism, we studied the effect of pretreatment with cyclophosphamide (CY) on the development of antitumor delayed-type hypersensitivity (DTH) reaction in the SMT-6-bearing SHR treated with Fr-5 (0.5 or 2.0 mg/kg). Treatment with 0.5 mg of Fr-5 per kg significantly increased the DTH reaction to SMT-6 cells in both CY-pretreated and untreated SHR. In contrast, treatment with 2.0 mg of Fr-5 per kg produced a significant antitumor DTH reaction in SHR pretreated with CY but failed to induce the DTH reaction in SHR untreated with CY. These results suggest that higher doses of Fr-5 may induce preferentially suppressor T-cells rather than killer T-cells in tumor-bearing SHR with congenital T-cell depression.