Suppression of cell‐mediated lymphocytotoxicity against minor histocompatibility antigens mediated by Lyt‐1⁺Lyt−2⁺ T cells of stimulator‐strain origin

Abstract

Cultured, unprimed spleen cells suppress the generation of cytolytic T lymphocytes when added to mixed lymphocyte culture of cells disparate at minor histocompatibility (H) loci. Cells cultured for 2 to 3 days inhibit cell-mediated lympholysis specifically in that they suppress only when they carry the same H antigen by which the stimulators activate the responding cells. However, culturing of cells for more than 3 days results also in the generation of nonspecific suppressor cells which inhibit the cell-mediated lympholysis regardless whether they carry the stimulating antigens. The specific suppressor cells are T lymphocytes of the Lyt-1+Lyt-2+ type. Fresh, uncultured spleen cells, although ineffective in vitro, can prevent the in vivo priming of minor H-specific cytotoxic T lymphocyte precursors when injected i.v. into mice incompatible at minor H loci. This suppressive effect of the immunizing inoculum is abolished by irradiation (3300 rds) or by treatment with a monoclonal Thy-1-specific antibody and complement. Thus the suppressor T cell demonstrated here is of the "veto" cell type; that is, it probably suppresses minor H-specific cells when the latter recognize the stimulating antigen on the surface of the suppressor cell itself.

Human CD4+ T Cells Displaying Viral Epitopes Elicit a Functional Virus-Specific Memory CD8+ T Cell Response

“…Furthermore, by using class I tetramers to identify and enumerate the Ag-specific CTLs, we were able to exclude a veto cell inactivation of Ag-specific antiviral CD8 ϩ T cells in our system. In contrast to earlier studies using CD8 ϩ T cells as APCs (22)(23)(24), we found that CD4 ϩ T-APCs have no veto activity. These results are in agreement with studies that have shown that Ag-specific secondary CTL responses are resistant to veto cell suppression in vitro (21).…”

“…In addition, the transfer of MHC-peptide complexes from APCs to CD4 ϩ T cells has been proposed in the mouse system to stimulate CD8 ϩ CTL responses (19,20). In contrast to the stimulatory effect observed by mouse Ag-presenting CD4 ϩ T cells (T-APCs), earlier studies have described the specific inhibition or vetoing of Ag-specific CTL responses by CD8 ϩ T cells bearing self-Ag (21)(22)(23)(24). In this study, we examined the functional consequences of viral epitope presentation by recently activated human CD4 ϩ T cells to the memory herpes virus-specific CD8 ϩ T cells.…”

Irreversible inactivation of activated cytotoxic T lymphocyte precursor cells by “anti‐self” suppressor cells present in murine bone marrow T cell colonies

“…Maki et al [13] and Gozzo et al [14] have shown that transfer of BM cells into anti-lymphocyte serumtreated recipient mice can prolong donor allogeneic skin graft survival. Rammensee et al [15] have shown that cells present in normal spleen, after being cultured in vitro without priming for 2-3 days, can specifically suppress the development of an in vitro cytotoxic response against their own minor histocompatibility antigens. The same cells appear to be capable of suppressing an in vivo response against their minor histocompatibility antigens.…”

Tolerance Induction in Presensitized Bone Marrow Recipients by Veto CTLs: Effective Deletion of Host Anti-Donor Memory Effector Cells

“…This activity is unique in the direction of recognition, i.e., the T cell to be inactivated bears the burden of recognition of the veto cell. Cells from a variety of tissues can mediate veto activity, including BM, thymus, spleen, lymph node, and fetal liver (9,10,(12)(13)(14). Various cell types have been isolated from these tissues and shown to mediate veto activity including T lymphocytes, NK cells, and dendritic cells.…”