Role of cytokines in the maintenance of the memory immune response induced by a rat histiocytoma in syngeneic hosts.

The nature of immune memory induced by a rat histiocytoma, AK-5, in syngeneic hosts was studied. AK-5 tumor when transplanted intraperitoneally (i.p.) into naive animals grows as ascites and is 100% fatal. However, spontaneous regression of AK-5 tumor was observed in 60% of animals upon s.c. transplantation. Interestingly, all the tumor-rejected animals (immune) were found to resist further i.p. challenges with AK-5 cells. The immunity thus developed is specific for AK-5 tumor, since other tumors grow in these animals. In order to understand the tumor-specific immune memory induced after AK-5 tumor transplantation, we have evaluated circulatory-cytokine profiles of i.p. tumor-transplanted naive and immune animals. Our results show an increase in the levels of IL-2, IL-12 and IL-4 in tumor-injected immune animals compared with normal animals, whereas the interferon-gamma levels were totally reversed in these two sets of animals. We also found elevated levels of circulating immune complexes in the sera from AK-5-rechallenged immune animals. We have also evaluated the cytotoxic potential of splenocytes and pure natural killer cells from immune animals rechallenged with AK-5 cells, and have found a significant increase in antibody-dependent cellular cytotoxicity. Similarly, in vitro proliferation of total splenocytes and nylon-wool non-adherent cells from immune animals was much higher compared with the normal animals. The present study thus suggests antigen-independent maintenance of clonal burst size, which could be the form of immune memory induced by AK-5 tumor in the syngeneic host.