EVIDENCE THAT IFN-7 IS RESPONSIBLE FOR NATURAL SUPPRESSOR ACTIVITY IN GVHD SPLEEN AND NORMAL BONE MARROW

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Abstract
Natural suppressor (NS) cells are capable of suppressing immunological responses in a nonspecific manner. Previously, we have described NS cells in the spleens of mice undergoing chronic graft-versus-host disease (GVHD) and also in normal B10.D2 bone marrow (BM). NS cells obtained from these environments appear dependent upon lymphokines for their ability to manifest suppression. In this report, with anti-IFN-.gamma. antibody, we show that IFN-.gamma. is necessary for NS cell activation. Anti-IFN-.gamma. antibody is able to remove the ability of NS cells to suppress a concanavalian A (Con A) proliferation assay. Also, anti-IFN-.gamma. antibody removes the ability of rIL-2, lectin-free Con A supernate (CAS), and recombinant IFN-.gamma. (rIFN-.gamma.) to enhance NS suppression of lipopolysaccharide response. By these criteria, IFN-.gamma. is required for NS cell activation, and rIL-2 may act indirectly by its ability to stimulate IFN-.gamma. synthesis. These results are discussed in the context of the immunosuppression seen in human BM transplantation.