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Synergistic Cooperation between Isoantiserum and Immune Lymphoid Cells: In Vitro Studies with a Syngeneic Rat Lymphoma¹

Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, California 90024

Abstract

The immune response of W/Fu rats to a syngeneic tumor was notable for the absence of serum-blocking activity and the presence of serum potentiation of cellular cytotoxicity (synergistic effect).

Heat-inactivated isoimmune serum potentiated the in vitro cell-mediated cytotoxicity (CMC) of lymphoid cells immune to a syngeneic Gross virus-induced lymphoma (C58NT)D in W/Fu rats. This isoimmune serum contains antibodies capable of mediating antibody-dependent cellular cytotoxicity (ADCC) in the presence of normal rat lymphoid cells. The synergistic effect observed demonstrated greater cytotoxicity than the sum of CMC and ADCC measured independently.

Inoculation of W/Fu rats with (C58NT)D tumor cells resulted in a 2- to 3-fold increase (compared to normal lymphoid cells) in the ADCC activity of immune spleen and peripheral blood cells. This was true for both the specific target cell (C58NT)D antibody complex and an unrelated target cell antibody complex. The kinetics of this increase in ADCC activity parallels the development of CMC activity as measured in vitro.

The synergistic effect is primarily attributable to an increased capacity of immune lymphoid cells to lyse antibody-coated target cells. The concomitant increase in Fc receptor-bearing cells (non-T cells) may contribute to this effect.

Footnotes

¹ This work was supported by Public Health Service Grant CA 12800 from the National Cancer Institute, National Institutes of Health, Bethesda, Maryland.