Veto Activity of Activated Bone Marrow Does Not Require Perforin and Fas Ligand

• DOI: 10.1006/cimm.2001.1771
• Publication Date: 2002-09-16T14:51:08Z
• Authors: Pavel Chrobak; Ronald E. Gress
• Keywords: Cytotoxicity, Immunologic; Pore Forming Cytotoxic Proteins; Mice, Inbred BALB C; Fas Ligand Protein; Membrane Glycoproteins; Time Factors; Perforin; Bone Marrow Cells; Mice, Transgenic; Mice, Inbred C57BL; Mice; 03 medical and health sciences; 0302 clinical medicine; Animals; T-Lymphocytes, Cytotoxic

Veto cells suppress generation of CD8(+) T cell immune responses in an antigen-specific manner, with specificity dictated by antigens on the veto cell surface. Activated bone marrow (ABM) veto cells belong to the NK cell type lineage and veto by clonally deleting antigen-specific precursor cytotoxic T cell lymphocyte (CTL). In vitro cytotoxicity of ABM depends largely on the perforin/granzyme and Fas/Fas ligand pathways. Utilizing perforin-deficient and functional Fas ligand-deficient gld mice as a source of ABM and functional Fas-deficient lpr mice as a source of precursor CTL, we demonstrate in this study that ABM cells utilize a perforin- and Fas-independent pathway to veto allogeneic cell-mediated cytotoxic responses. We also show that ABM cells mediate perforin- and Fas-independent veto activity even in an 8-h clonal deletion assay. We conclude that ABM veto activity does not require the two primary pathways of cell-mediated death.