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Studies of the Mechanisms for the Induction of in Vivo Tumor Immunity

III. Recruitment of Host Helper Cells by Donor T Cells in Adoptive Transfer of Cell-Mediated Immunity¹

From the Laboratory of Cell Biology, National Cancer Institute, Bethesda, Maryland 20014, and the IIIrd Department of Internal Medicine, Osaka University Medical School, Fukushima, Osaka 533, Japan

Abstract

In studying the cell-mediated immunity to FBL-3, a Friend virus-induced leukemia syngeneic to C57BL/6 mice, it was found that the levels of cytotoxic response induced by the in vivo adoptive transfer experiments were always considerably higher than those induced by the in vitro mixed lymphocyte tumor cell culture (MLTC). This was especially true in using lymph node cells as responders. Further investigation showed that this difference was not due to the generation of suppressor cells in vitro or to the lack of precursor killer cells in lymph nodes. During in vivo sensitization, it appeared that helper cells were recruited by T cells to augment the cell-mediated cytotoxic response. In the in vivo experiments, pretreatment of the recipient hosts with antimacrophage agents (silica or carrageenan) caused significant reduction of cytotoxic response induced in the adoptive transfer experiments; the effect was more pronounced on the adoptive transfer of lymph node cells than spleen cells, indicating that macrophages are needed for generating an efficient in vivo T cell-mediated immunity. In the in vitro experiments, it was found that the peritoneal cells or spleen cells from normal x-irradiated syngeneic mice could also augment the MLTC reactions, thus, these helper cells were presumably macrophages. The lack of sufficient supply of exogenous macrophages could be one of the major cause of the low level of cytotoxic response generated by in vitro sensitization. This is especially true for the lymph node cells that have more stringent dependency on the presence of excess amounts of macrophages. These results indicate that recruitment of macrophage-like helper cells may play an important role in the induction of an efficient in vivo tumor immunity.

Footnotes

¹ Supported by a grant from the Japan Society for the promotion of Science.