Immune reactivity in SL2 lymphoma-bearing mice compared with SL2-immunized mice

Summary We have studied the rather paradoxical phenomenon of the growth of an antigenic tumor in an immunocomponent host. This phenomenon was studied by comparing (a) the lymphocyte reactivity and (b) the macrophage cytotoxicity, during SL2 growth in DBA/2 mice (SL2-bearing mice) and in DBA/2 mice immunized against SL2 tumor cells (SL2-immune mice). Immune mice rejected a challenge of tumor cells. The immune T-lymphocytes rendered macrophages cytotoxic (arming) and were able to transfer tumor resistance to naive animals. Nonimmunized mice did not reject a challenge of SL2 cells. In these tumor-bearing mice various forms of immune reactivity were tested. Lymphocytes with the capacity to arm macrophages could not be found in the lymphoid organs. However, lymphocytes isolated from the tissue directly surrounding the subcutaneous SL2 tumor could arm macrophages in vitro.Shortly after subcutaneous tumor grafting cytotoxic macrophages were found in the peritoneal cavity. In the serum macrophage arming factors were detected that rendered macrophages cytotoxic in vitro. This cytotoxicity of the peritoneal macrophages and the presence of macrophage arming factors in the serum showed a similar biphasic pattern. The first phase of cytotoxicity between day 3 and 8 after tumor grafting was tumor (SL2) specific. The second phase from day 12 and onwards was not tumor specific. During the first 4 days after SL2 grafting the DBA/2 mice expressed a specific concomitant immunity to a second tumor graft. Then 7 or more days after grafting the first SL2 tumor, the concomitant immunity was nonspecific as the growth of a second SL2 tumor graft and a L5178Y (DBA/2) tumor graft were inhibited. In addition, the immune suppressive activity of serum and lymphocytes was tested. Neither serum nor lymphocytes from SL2-bearing mice suppressed the macrophage arming capacity of SL2 immune lymphocytes. Lymphocytes from tumor-bearing mice did not inhibit the capacity of SL2-immune lymphocytes to transfer resistance to naive animals. On the contrary, lymphocytes obtained from SL2-bearing mice 14 days after SL2 grafting transfered tumor resistance in a Winn-type assay. These data suggest that the growth of an antigenic tumor is due to the inability of the immune system to mount an effective antitumor effector cell population during tumor growth, rather than an immune suppression of the antitumor reactivity, as a limited immune reactivity could be detected in tumor-bearing mice, whereas immune suppression could not be detected.