Correlation Between Lymphocyte-Induced Donor-Specific Tolerance and Donor Cell Recirculation

Abstract

SnnlnlaryIntravenous infusion of mice with major histocompatibility complex (MHC) incompatible lymphocytes can inhibit the response of recipient T cells capable of recognizing the injected cells, and can enhance survival of grafts sharing MHC with the injected cells. However, neither T cell inactivation nor graft survival enhancement is always achieved. This is particularly true for donor cells that are fully allogeneic (as compared to semiallogeneic) to the recipient. We show here that both donor-specific induced response reduction and graft survival enhancement are directly correlated with the ability of the injected lymphoid cells to persist in the recirculating lymphocyte pool of the host. Whether donor cells persist correlates inversely with the level of natural killer cell (NK) activity in the host. Fully allogeneic cells can only persist in hosts with low NK activity and can then induce response reduction. Both persistence and response reduction are abrogated by injection of the host with polyI:C, a treatment that boosts host NK activity. The same treatment also destroys the ability of semiallogeneic injected cells to persist, to induce response reduction, and to enhance skin graft survival.

Do maternal cells trigger or perpetuate autoimmune diseases in children?

“…Alloreactive CTL and NK cells are crucial for the elimination of foreign cells after solid organ or stem cell transplantation [57]. NK cells, abundant in fetal blood, would be inhibited by HLA Class I molecules on maternal cells that are shared by the child, preventing elimination of MMc [58].…”