Some new perspectives on transplantation immunity and tolerance

Presentation of the H-Y antigen on Langerhans' cell-negative corneal grafts downregulates the cytotoxic T cell response and converts responder strain mice into phenotypic nonresponders.

“…Elimination of alloreactivity is achieved only by removing la' APC from both responder and stimulator cell populations (24), which indicates that cell surface alloantigens can be presented by APC from the stimulator cell population (direct primed response) or, after reprocessing, by APC from the responder population (cross-primed response). Understanding the mechanisms of direct priming versus cross-priming are essential for transplantation immunology since current attempts to improve allograft survival both experimentally and clinically often include the putative removal of APC from the graft (23,25). We have used the murine cornea as an allograft model to investigate the role of graft-derived LC during the induction of host CTL responses to the H-Y antigen.…”

“…Presentation of H-YAntigen on LC-Grafts Downregulates the Anti-H-Y CTL Response. The possibility that presentation ofthe H-Y antigen on APC-deficient grafts resulted in active suppression (23) was investigated in cell mixing experiments. The results summarized in Table VI show the secondary CTL responses of individual mice immunized with HY presented on LC-or LC' corneal grafts .…”

Reprogramming the Immune System for Peripheral Tolerance with CD4 and CD8 Monoclonal Antibodies

“…In other words, peripheral tolerance in vivo has interacting componentsone is the responsive state of the T cells, which must be reduced in tolerant mice otherwise they would not accept repeated donor type grafts -but the other is the state of the target tissue, where a fresh graft must be more susceptible to our attempts to break tolerance compared to an established graft. We know that established grafts are still capable of being rejected, despite the known loss of donor type dendritic cells {Silvers 1984, Silvers et al 1987): if we first depleted the T cells from tolerant animals and later infused syngeneic tiaive spleen cells then these grafts were rejected promptly. The fact that tolerance of the original skin graft is maintained on an individual mouse which is actively rejecting a genotypically-identical graft at the same point in time therefore strongly argues for a local regulatory mechanism of peripheral tolerance.…”

Cellular mechanisms: Induction of heart allograft survival in rats by 15-deoxyspergualin

“…The results show that the MLR in LEW spleen cells to donor party (ACI) and third party (Wistar) stimulator spleen cells were inhibited in a cell-dose-dependent manner. As various mechanisms of graft survival, such as the modulation of graft antigen expression [6,14], depletion of clonally active cells following immunosuppression and exposure to the graft [7,8], antigen/antibody blockade of effector cells [15,16], activation of suppressor cells [3,13],and production of suppressor humoral factor(s), have been postulated. Our results strongly suggest that DSG may fail to affect suppressor cells, and these cells may progressively develop and play a partial role in continuing allograft survival states.…”