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

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Abstract
Treatment with a combination of recombinant human interleukin-2 (rHIL-2) and recombinant mouse interferon-beta (rIFN-.beta.) or -gamma (rIFN-.gamma.) 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-.beta. caused regression of the tumor but the combination of rHIL-2 and rIFN-.gamma. 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-.beta. than by the combination of rHIL-2 and rIFN-.gamma.. 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, Lyt2+/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-.beta., the Lyt2+/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-.gamma.. Thus, injections of rHIL-2 and rIFN-.beta. 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.

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