INDUCTION OF HAPTEN-SPECIFIC T-CELL TOLERANCE BY USING HAPTEN-MODIFIED LYMPHOID-CELLS .1. CHARACTERISTICS OF TOLERANCE INDUCTION

Abstract

BALB/c mice were made tolerant to the T [thymus-derived] cell-dependent phenomenon of contact sensitivity to DNFB [dinitrofluorobenzene] by i.v. injection of syngeneic lymphoid cells which were previously modified with DNFB in vitro. The highly efficient unresponsiveness, as measured by ear challenge and in vitro antigen-induced cell proliferation, followed dose-response kinetics in vivo and in vitro, and was exquisitely specific for the DNP [dinitrophenol] moiety. The kinetics of tolerance induction were very rapid and were previously shown to be long lasting. Unresponsiveness was more efficient when the hapten-modified cells were introduced by the i.v. route, and tolerance could be increased by repeated injection of tolerogen. The tolerance could be transferred to normal syngeneic recipients by spleen and/or lymph node cells from tolerant donors. A wide variety of hapten-modified lymphoid cells, including mixed cell populations and enriched populations of T cells, B [bone marrow-derived] cells and macrophages, were capable of inducing tolerance. The unresponsiveness was dependent merely on the association of DNP to the lymphoid membrane proteins and not upon the viability of the hapten-modified cells. In hapten-specific T cell sensitivity, as exemplified by contact sensitivity to DNFB, specific T cell tolerance is probably actively induced by hapten on self-membrane. In other hapten-specific antibody-forming systems, tolerance appears to be most readily induced by hapten on soluble self protein or on a nonimmunogenic carrier.