Subject(s)
Antineoplastic Agents/pharmacology , Interleukin-2/biosynthesis , Lymphocytes/immunology , Animals , Cyclophosphamide/pharmacology , Doxorubicin/pharmacology , Female , Lomustine/pharmacology , Lymphocytes/drug effects , Lymphocytes/radiation effects , Male , Melphalan/pharmacology , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Inbred C57BL , Spleen/immunology , X-RaysABSTRACT
Splenocytes of normal (NS) and tumor-bearing (TBS) mice (Balb/c, C57BL/6, C3H) were stimulated in vitro for 24 h with concanavalin A and the amount of T cell growth factor (TCGF) generated was measured. TBS of mice carrying subcutaneous implants (greater than 1 cm tumor diameter) of several T lymphomas, pulmonary and mammary carcinomas, and a melanoma, or intraperitoneal implants (greater than 10(8) cells) of ascitic lymphomas produced (per culture) 40-90% less TCGF than that generated by NS. TBS also contained a greater proportion of phagocytic cells and a higher ratio of Lyt 2+/Lyt 1+ T cells as compared with NS. In cocultures consisting of NS and TBS (1:1), TCGF production by NS was markedly suppressed. In contrast, addition of up to 30% tumor cells to NS decreased production only slightly. Removal from TBS of either phagocytes or Lyt 2+ T cells, or treatment in vitro with indomethacin [IND; an agent inhibiting prostaglandin (PG) synthesis], appreciably reduced their capacity to inhibit NS and improved TCGF production in TBS cultured alone. TCGF production by TBS could be completely restored by depletion of both phagocytes and Lyt 2+ T cells. Elevated quantities of TCGF (up to threefold) were generated by TBS of mice pretreated in vivo 1-4 days previously with low doses of either cyclophosphamide or X-irradiation, with or without IND. It is concluded that suppression of TCGF production in vitro by TBS is mediated by phagocyte-released PG and by Lyt 2+ T lymphocytes.
Subject(s)
Interleukin-2/biosynthesis , Lymphocytes/immunology , Neoplasms, Experimental/immunology , Animals , Cells, Cultured , Concanavalin A/pharmacology , Female , Mice , Mice, Inbred Strains , Phagocytes/immunology , Prostaglandins/immunology , Spleen/immunology , T-Lymphocytes/immunologyABSTRACT
A murine carcinoma cell line was grown in a microcarrier culture and was used for immunization of allogeneic mice. It was found that inoculation of cells attached to microcarrier beads resulted in heightened serum titers of cytotoxic antibodies and in a stronger cell-mediated cytotoxic reactivity in the spleen compared to cells detached from the substrate. It is proposed that immunization of animals with anchorage-dependent cells should be carried out while the cells are still adherent to the culture microcarriers.
