Suppression by tumor growth of T cell growth factor production in mouse lymphoid cell cultures

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.