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Cellular Cytotoxicity and Serum Inhibition in Normal Mice following Transfer of Xenogeneic Tumor-sensitized Cells¹

Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261

Findings from previously reported investigations revealed that lymphoid and myeloid cells from tumor-bearing mice, when transferred to normal syngeneic mice never exposed to a tumor, imparted "information" which resulted in the production of tumor-specific cytotoxic cells by recipients. The present studies determined the cytotoxicity of cells from normal mice which were recipients of cells obtained from rats (xenogeneic) sensitized to mouse tumor. Normal rat lymph node cells (LNC) or spleen cells (SPC), when evaluated prior to their transfer, were found to be noncytotoxic to tumor target cells. LNC or SPC from rats sensitized to mouse tissue, either normal or tumor, were highly cytotoxic. Subsequent to the transfer of LNC or SPC from normal rats or from those sensitized to H-2 antigen (normal mouse tissue), little or no cytotoxicity was identified in LNC, SPC, or macrophages cultured from bone marrow cells of normal recipient mice. When the transferred cells were derived from rats sensitized to both H-2 and tumor antigen, i.e., tumor cells, and the target cells were from the same tumor used for sensitization, maximal cytotoxicity was demonstrated in cultured macrophages, LNC, and SPC of normal mouse recipients. An increase in cellularity of recipient nodes, spleen, and bone marrow occurred following transfer of tumor-sensitized xenogeneic cells, unsensitized rat cells, or those cells sensitized to normal mouse spleen, indicating an equivalent recruitment of host cells by all types of xenogeneic cells transferred. The behavior of the recruited cells, i.e., tumor cytotoxicity, was entirely dependent upon the use of tumor for sensitization of donor cells. Findings similar to those in the syngeneic system indicate that sera from normal cell recipients inhibit the cytotoxicity of cells derived from tumor-bearing animals. The findings indicate that information has been transferred by tumor-sensitized xenogeneic cells to normal animals that have never been exposed to tumor cells, which results in their production of tumor-specific cytotoxic cells. H-2-sensitized xenogeneic cells failed to produce such an effect. The relation of these findings to the use of xenogeneic cells for passive tumor immunotherapy is commented upon.

¹ Supported by USPHS Grants CA-14972 and CA-12102 and funds contributed by Mr. and Mrs. Luis Nunez of Caracas, Venezuela.

² To whom requests for reprints should be addressed, at Department of Surgery, University of Pittsburgh School of Medicine, 914 Scaife Hall, 3550 Terrace Street, Pittsburgh, Pa. 15261.

Received 7/10/79. Accepted 8/22/79.