Cycling of Immune Responses to a Syngeneic Murine Mammary Adenocarcinoma

Abstract

Fischer rats immunized i.p. with 10³ to 10⁷ syngeneic 13762A mammary adenocarcinoma tumor cells develop a biphasic cytolytic response to the tumor in the spleen. The first (early) cytolytic phase, detected within 4 days of tumor inoculation, peaks on Day 7 and decreases by Day 9. The second (late) cytolytic phase is detected 13 or more days after tumor injection and is maintained until death. Spleen cells obtained 9 to 13 days after inoculation of the 13762A mammary adenocarcinoma lack cytolytic activity and specifically inhibit in vitro generation of cytolytic lymphocytes. The magnitude of either splenic cytotoxicity or suppression is independent of the initial tumor dose. Both early and late cytolytic cells are T-lymphocytes. Cytolysis by early spleen cells is less specific than that by late cytolytic cells, since early lymphocytes lyse a second unrelated F344 mammary adenocarcinoma, R3230. Neither spleen cell population lyses a Moloney sarcoma-induced tumor or a fibrosarcoma from syngeneic rats.

Serological blocking factors are detected in 13762A tumorbearing rats within 4 days following injection of 10⁴ tumor cells. Blocking activity in Day 12 serum appears on Sephacryl S-200 in the immunoglobulin G (IgG) (M.W. 160,000) and low-molecular-weight (M.W. < 70,000) fractions. Blocking activity in Day 20 serum is more polydispersed, separating into the high-molecular-weight (M.W. ≥ 200,000), IgG, and low-molecular-weight fractions. The high-molecular-weight and low-molecular-weight blocking factors probably represent immune complexes and free tumor antigen, respectively; both factors similarly inhibit early and late cytolytic cells. The IgG blocking factor in Day 12 serum, tentatively identified as an anti-receptor antibody, preferentially inhibits the early cytolytic cells; Day 20 IgG preferentially inhibits the late cytolytic cells. Finally, Day 11 suppressor cells preferentially inhibit generation of cytolytic lymphocytes from the early spleen cell population.

These results suggest that the host response to this syngeneic tumor is complex and alternates between phase of cytolytic activity and suppression of the immune response. The cytolytic cells obtained during different phases appear to vary in their ability to be inhibited by both the IgG blocking factors and suppressor cells.