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-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, 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-beta, 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-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.
Iigo
M
M
Chemotherapy Division, National Cancer Center Research Institute, Tokyo.
Nishikata
K
K
Nakajima
Y
Y
Moriyama
M
M
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy; D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D007167:Immunotherapy; D007370:Interferon Type I / Q000008:administration & dosage* / Q000627:therapeutic use; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000627:therapeutic use; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000627:therapeutic use; D007958:Leukocyte Count; D008099:Liver / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology* / Q000628:therapy; D009929:Organ Size; D010529:Peritoneal Cavity / Q000473:pathology; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D013154:Spleen / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology
D000950:Antigens, Ly; D000954:Antigens, Surface; D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D016899:Interferon-beta; D007371:Interferon-gamma; D000068556:Interferon beta-1a