Recirculating, suppressor T cells in transplantation tolerance.

Abstract

An adoptive transfer system was used to examine the capacity of cellular inocula from rats fully tolerant of Ag-B antigens to transfer tolerance to irradiated recipients. Permanent tolerance in these irradiated recipients involved specific suppression of the regenerating immune response. Cells obtained from tissues rich in recirculating lymphocytes were the most effective suppressors. Highly purified inocula of T cells from tolerant donors were potent suppressors in irradiated hosts, but were not capable of direct suppression of peripheral antigen-sensitive T cells.. The role of the thymus in maintaining the complement of recirculating suppressor T cells in tolerant animals was examined after adult thymectomy. Thymectomized tolerant rats did not reject their tolerated grafts, and the longevity of the suppression in tolerant rats was confirmed by showing that adoptive transfer of cells from thymectomized tolerant donors was effective in suppressing irradiated recipients up to 180 days after thymectomy. Cellular inocula from these donors appeared to lose their suppressor function marginally faster than they lost effector function (as measured by their capacity to mediate rejection of third party control grafts). Thymectomy made tolerant rats more vulnerable to the termination of tolerance by challenge with normal cells. Transplantation tolerance is maintained in adult rats by long-lived rapidly recirculating suppressor T cells. The target for the suppressor action of these cells is probably the precursor of alloantigen-sensitive lymphocytes, and the effect of suppression may be deletion or inactivation of the relevant clone of these cells.

Regulatory T cells in the establishment and maintenance of self-tolerance: role of the thymic epithelium

“…Our experiments of tolerance transfer by injection of peripheral T cells point out a crucial role of regulatory T lymphocytes in the maintenance of self tolerance (Modigliani et al, 1995a, b). Suppressive mechanisms in transplantation tolerance were previously suggested by Kindred A B (1971) and by Dorsch and Roser (1977). Since these results, the presence in the periphery of T cells, able to prevent autoaggressive immune reactions, has been established (see for review : Annacker et al, 2001;Wood and Sakaguchi, 2003).…”

Simultaneous LFA-1 and CD40 Ligand Antagonism Prevents Airway Remodeling in Orthotopic Airway Transplantation: Implications for the Role of Respiratory Epithelium as a Modulator of Fibrosis

“…The underlying principle of adoptive transfer assays is that it is often possible to demonstrate immune tolerance to donor Ags by reconstituting the immune system of a second transplanted immunodeficient animal with immune cells from the originally transplanted animal (22). Non-reconstituted immunodeficient animals normally have no capacity to reject a transplant in the absence of lymphocytes.…”

Functional clonal deletion in immunological tolerance to major histocompatibility complex antigens.

“…Originally, it seemed logical to ascribe tolerance to an elimination of potentially self-reactive lymphocyte clones through early contact with antigen, a view that has subsequently received substantial (2, 3) but not unchallenged (4,5) experimental support. Since the discovery of suppressor T lymphocytes (6), it has been amply documented that these play a role in several different models oftolerance involving MHC antigens (7)(8)(9)(10)(11)(12)(13). Given that a lymphocyte population containing suppressor T cells may effectively inhibit the activation of normal immunocompetent cells ("infectious tolerance"), it becomes a matter of some difficulty to determine the presence or absence of functional T lymphocytes within a population whose phenotype is suppressor.…”