Adjuvant-induced thymus-derived suppressor cells of cell-mediated tumour immunity

Abstract

THE use of immunoadjuvants in enhancing immune responses to various antigens and particularly in tumour therapy is based largely on the concept that an increased level of specific immunity may be achieved by nonspecific stimulation of the immune system1. However, the tumour-protective effect of adjuvants has not been entirely consistent in all systems studied, and also, an immune suppressive effect of adjuvants has been demonstrated mainly by using in vitro assays of cell-mediated immunity2. It remains to be determined whether a defect measured by such general tests of lymphocyte function may also represent an indication of depressed cell-mediated immunity against the progressive growth of tumours. Moreover, the target cell in the immune system for adjuvant effect has not been characterised clearly. Our laboratory has made extensive study of immune response to SV40-induced syngeneic transplantable MKSA cells of BALB/c mice3–5. This tumour has been shown to possess tumour-associated antigens which can immunise specifically against the growth of MKSA cells. The role of T lymphocytes in the immune response against SV40-induced tumour-associated antigens was shown by in vivo tumour cell neutralisation assay (Winn)6 and by in vitro 51Cr release assay7. We now report that injection of complete Freund's adjuvant (CFA), one of the most useful adjuvants in enhancing immune responses, markedly inhibited the ability of immune spleen cells to prevent SV40-induced tumour growth in the Winn assay and to lyse SV40-transformed cells in the cytotoxicity assay. Moreover, untreated mice which reject suboptimal numbers of tumour cells die of progressive tumour growth following treatment with CFA and tumour cells; adult thymectomy reverses the suppression caused by CFA; and the target cell for CFA effect is the T lymphocyte. These data suggest that treatment with CFA causes depression of specific anti-tumour cell-mediated immunity by activation of suppressor thymus-derived lymphocytes.