Changes in Lymphocyte Subsets Following Multiple Administration of Recombinant Interleukin‐2 plus Recombinant Interferon‐beta or ‐gamma in Tumor‐bearing Mice

Treatment with a combination of recombinant human interleukin‐2 (rHIL‐2) and recombinant mouse interferon‐beta (rIFN‐β) or ‐gamma (rIFN‐γ) showed a significant antitumor effect against sc adenocarcinoma 755 in mice, although treatment with either one alone had almost no effect. The combination of rHIL‐2 and rIFN‐β caused regression of the tumor but the combination of rHIL‐2 and rIFN‐γ did not. Injection of tumor‐bearing mice with the combinations of rHIL‐2 and rIFN resulted in marked increases in the total number of peritoneal lymphocytes, and the frequency of Lyt‐2(+) cells was more markedly increased by the combination of rHIL‐2 and rIFN‐β than by the combination of rHIL‐2 and rIFN‐γ. In Winn assay, elimination of the Lyt‐2(+) population abolished the protective capacity of the peritoneal cells. The subsets of thymocytes were drastically changed when mice were bearing a tumor or were treated with cytokines. In particular, Lyt‐2(+)/L3T4(+) cells were decreased in tumor‐bearing mice, but many Lyt‐2(+)/L3T4(+) cells were maintained in the thymus by treatment with a cytokine alone. When treated with rHIL‐2 and rIFN‐β the Lyt‐2(+)/L3T4(+) cells were markedly decreased, while Lyt‐2(‐)/L3T4(‐) T‐cells were increased, but these subsets were little changed by treatment with rHIL‐2 plus rIFN‐γ. Thus, injections of rHIL‐2 and rIFN‐β into tumor‐bearing mice resulted in a high frequency of Lyt‐2(+)/L3T4(‐) cells in the peritoneal cavity, together with changes in the T‐cell subsets in the thymus. These results suggest that maturation of T‐cells in the thymus may be an important step in the pathway by which cytokine treatment brings about regression of tumors.