Changes in the host natural killer cell population in mice during tumor development. 1. Kinetics and in vivo significance.

Our earlier studies revealed an increase in the level of null (surface IgM-negative, Thy 1-negative) lymphocytes in mice shortly after tumor transplantation and before the clinical appearance of spontaneous mammary tumors. The present study examined the splenic natural killer (NK) cell activity as well as the incidence of NK lineage cells in these hosts, since NK cells are considered to be a subset of null lymphocytes. Splenic NK activity against YAC-1 lymphoma targets was measured with a 4-hr 51Cr-release assay in CBA mice transplanted ip with 10(6) Ehrlich ascites tumor (EAT) cells, in elderly C3H mice prior to and during the growth of spontaneous mammary tumors (SMT) and in young C3H mice transplanted sc with 5 X 10(6) SMT cells or 10(6) cells from two syngeneic mammary tumor lines (T-58 and MT-2) of recent origin. In EAT-transplanted mice total NK activity in the spleen increased rapidly to a peak (11-fold) at 3 days, coincident with the null cell rise, but then declined to subnormal levels by Day 7 when the null cell level was still high. A similar pattern of activity was exhibited by intratumor lymphocytes isolated from the EAT. In SMT-transplanted mice splenic NK activity showed a small rise at Day 3, followed by a drop to below normal at Day 7, subnormal levels lasting for the tumor life span. Similar results were noted in T-58- or MT-2-transplanted mice. Null lymphocytes recovered during the peak NK activity from the spleen of 3-day EAT-bearing mice, when mixed with 10(6) EAT cells at 25:1 E:T ratio and adoptively transferred into fresh mice in a Winn type assay either ip or sc, completely prevented tumor development indicating a high enrichment of NK cells functionally effective in vivo. Elderly clinically tumor-free C3H mice showed measurable NK activity, which dropped after the appearance of spontaneous mammary tumors to very low levels, the magnitude of decline rising with increasing tumor age (1-11 weeks) or size. The incidence of NK lineage cells was measured from the tumor target (YAC-1 lymphoma)-binding ability of the splenic null cells, identified with a radioautographic technique. Null target-binding cells (TBC) were NK-1+ and included both active as well as inactive NK lineage cells.(ABSTRACT TRUNCATED AT 400 WORDS)