CD4+8- T lymphocytes with potent antitumor activity in vivo were obtained in peritoneal exudate cells by immunizing mice with irradiated MM48
tumor cells admixed with
OK-432. These immune CD4+ T cells were used in adoptive immunotherapy for prevention of
lymph node metastases after removal of the primary
tumor. Complete cure of
metastases was obtained by adoptive transfer of CD4+ T cells admixed with irradiated MM48
tumor cells, but not by CD4+ T cells alone. To analyze the curative effect of admixing
tumor cells on the prevention of
metastases, a model of 1-day
tumor inoculated with macrophages was used. Administration of immune CD4+ T cells alone resulted in the regression of local
tumor in more than half of the mice, although all of them eventually died of
lymph node metastases. On the other hand, adoptive transfer of immune CD4+ T cells plus irradiated
tumor cells resulted in the complete regression of local
tumors in all the mice, which survived without any sign of
metastasis. The curative effect of the immune CD4+ T cells obtained by admixing irradiated
tumor cells was
tumor-specific. Macrophages induced by
OK-432 (tumoricidal), implanted together with
tumor, assisted
tumor regression more than did macrophages elicited by
proteose peptone (non-tumoricidal) in the same adoptive transfer system. Administration of recombinant
interleukin-2 instead of stimulant
tumor cells did not enhance, but rather eliminated the constitutive antitumor activity of CD4+ T cells. On the other hand, exogenous recombinant
interleukin-1 was more effective in the enhancement of antitumor activity of the CD4+ T cells as compared with stimulant
tumor cell administration. In this case, the activating states of macrophages at the implanted
tumor site had no influence on the therapeutic efficacy. A possible role of macrophages for induction of
tumor-specific cytotoxic T cells that were mediated by
tumor-specific CD4+ T cells is discussed.