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Suppression of Tumor-specific Cell-mediated Cytotoxicity by Immunoregulatory -Globulin and by Immunoregulatory -Globulin-like Peptides from Cancer Patients¹

Departments of Pathology [B. S. W.] and Surgery [J. A. M.], Harvard Medical School, Peter Bent Brigham Hospital, Boston 02115, and Departments of Microbiology [A. M. B.], Biochemistry [R. B. N., K. S.], and Medicine [S. R. C.], Boston University School of Medicine, University Hospital, Boston, Massachusetts 02118

The suppression of tumor-specific cell-mediated cytotoxicity by human immunoregulatory -globulin (IRA), by a peptide fraction derived from IRA, and by IRA-like peptides from the serum of cancer patients was studied in a syngeneic murine tumor-host system. Splenic lymphocytes from tumor-immunized mice were cytotoxic to specific tumor cells in vitro as measured by the [¹²⁵I]iododeoxyuridine release microcytotoxicity assay. However, this effect was significantly depressed if 1.25 to 5 mg of IRA per ml were added to the cultures. Pooled lyophilized normal human serum protein was inactive. IRA peptide and IRA-like peptide fractions from cancer patients were also highly suppressive of cell-mediated cytotoxicity at much lower concentrations (0.05 to 0.5 mg/ml). Control human serum peptide, which failed to inhibit the induction of hemolytic plaque-forming cells in sheep erythrocyte-injected mice, had no effect on cell-mediated cytotoxicity. IRA and IRA-like peptide fractions were not cytotoxic to the effector lymphocytes or to the target cells at the concentrations used.

¹ This work was supported by USPHS Grants CA-21644, CA-15848, CA-15129, CA-12209, and GM-10374.

² To whom requests for reprints should be addressed at the Department of Surgery, Harvard Medical School, Peter Bent Brigham Hospital, 721 Huntington Avenue, Boston, Mass. 02115.

Received 1/20/77. Accepted 5/20/77.