担癌ラットにおける宿主免疫能の変化とそのLAK細胞に及ぼす影響の解析

Alteration in immunoreactivity associated with tumor-bearing is well recognized ; however, the mechanisms of immunoregulation are still elusive, and little is known about their effects on immunotherapy with the use of lymphokine-activated killer(LAK) cells. A rat subcutane- ous tumor-host model using a gliosarcoma cell line(T9) syngeneic to F344 rats was established, whereby alteration in the proliferation or cytotoxic activities of spleen cells of tumor-bearing hosts were assessed, and subsequently its cellular as well as humoral mechanisms and also its effects on the induction and cytotoxicity of LAK cells were analyzed. The rats showed splenomegaly with the growth of the tumor with more than a 2-fold increase in spleen cell number for 2wks of tumor- bearing, which was sustained thereafter ; however, the spleen cells of advanced(longer than 3 wks) tumor-bearing rats showed impaired reactivity to Con A and LPS stimulation and in MLTC and MLC, although no constitutional change was recognized in the spleen cell populations. The natural cytotoxic activities of the spleen cells were minimally affected as assessed by cytotoxicity against K562 or T9 tumor cells. Induction of LAK activity in the spleen cells of tumor-bearing rats showed apparent inhibition with the growth of the tumor. The presence of suppressor cells in the spleens of advanced tumor-bearing rats was demonstrated as they suppressed proliferative responses of normal spleen cells to Con A stimulation and in MLTC and MLC, which were free of MHC restriction. Those suppressor cells could also interfer with the induction of LAK cells, but not with the effector phase of LAK cells. Negative and positive cell selection experiments revealed suppressor cells to be of two kinds : plastic adherent cells, of which 70% were macrophages and monocytes, and CD5(-) CD8(+) T cells, both of them could suppress not only the proliferative responses of lymphoid cells, but also the induction of LAK cells. Serum of normal rats and rats bearing the T9 tumor from initiation to 4wks showed a similar degree of dose dependent suppression on cell proliferative responses regardless of tumor-bearing or its period. Induction of LAK cells was more strongly inhibited by serum showing parallel relation to the growth of tumor at more than 0.1% concentration. These data indicated that immunosuppressive mechanisms were generated in the late tumor-bearing rats which preferentially supress cell proliferative responses and induction of LAK cells by two types of suppressor cells, plastic adherent cells and CD5(-) CD8(+) T cells. Serum inhibited lymphoid cell proliferation regardless of tumor-bearing, but suppression of the induction of LAK cells depended on the time of tumor-bearing