Natural Cytotoxic Cells against Solid Tumors in Mice

Abstract

Abstract Lymphohemopoietic cells from normal mice show cell-mediated cytotoxicity (CMC) against syngeneic or allogeneic chemically induced fibrosarcomas, when tested in a 24-hr cytotoxicity assay with 3H-proline pre-labeled adherent target cells. When two BALB/c tumors, Meth A, and Meth 113 were studied, spleen cells from syngeneic normal donors showed high CMC against Meth A and no CMC toward Meth 113. However, Meth 113 was susceptible to natural CMC by spleen cells from other mouse strains or PHA-induced CMC by syngeneic spleen cells. Other solid tumors tested showed variable patterns of susceptibility-resistance to natural CMC, whereas normal fibroblasts were negative. Susceptibility to natural CMC does not correlate with expression of murine leukemia virus-related antigens. Established lines are more susceptible to natural CMC than secondary tumor cultures, although susceptibility-resistance appear as stable properties of the targets. All the mouse strains and sublines tested showed natural CMC against the Meth A target; however, only a few strains (A/J, CBA/HN, NZB, and C3H/He) showed natural CMC against Meth 113. Natural CMC against Meth 113 of (BALB/c × A/J) F1 spleen cells is dominant, and the hybrid behaves like the reactive A/J parent. Natural cytotoxic (NC) cells are detected in nude mice in a BALB/c or CBA/H background (and also in CBA/HN mice, which have a B cell defect). The tissue distribution of NC cells shows high activity in spleen and marrow, with lower activity in lymph nodes, peritoneal washings, and thymus. Peritoneal exudates induced by complete Freund's adjuvant or BCG show high NC cell activity. NC activity in spleen was detected from birth and does not seem to decay with age (even at 1 or 2 years of age). The described characteristics of the NC cell have some similarities (and some discrepancies) with the natural killer (NK) cell described against T lymphoma targets. The differences include: 1) strain distribution; 2) appearance at birth; 3) no decay with age, and 4) to some extent, tissue distribution (i.e. both systems show high activity in spleen; however, NC cells are detected in thymus whereas NK cells are not). The similarities include: 1) susceptibility not related to expression of murine leukemia virus antigens; 2) no H2 restriction of cytotoxicity; 3) activity present in nude mice (and CBA/HN); 4) reactivity dominant in F1 hybrids, and 5) increase activity in peritoneal exudates after BCG administration. It seems possible that these systems may act as anti-tumor surveillance devices.