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The Induction of Hapten-Specific T Cell Tolerance by Using Hapten-Modified Lymphoid Cells

I. Characteristics of Tolerance Induction¹

From the Division of Clinical Immunology, Departments of Medicine and Microbiology, the University of Colorado School of Medicine, Denver, Colorado 80220

Abstract

BALB/c mice were made tolerant to the T cell-dependent phenomenon of contact sensitivity to DNFB by i.v. injection of syngeneic lymphoid cells which had been previously modified with DNFB in vitro. The highly efficient unresponsiveness, as measured by ear challenge and in vitro antigen-induced cell proliferation, was shown to follow dose-response kinetics both in vivo and in vitro and to be exquisitely specific for the DNP moiety. The kinetics of tolerance induction were shown to be very rapid and had been 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 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.

These experiments support the hypothesis that in hapten-specific T cell sensitivity, as exemplified by contact sensitivity to DNFB, specific T cell tolerance in 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.

Footnotes

¹ This work was supported in part by National Institutes of Health Grants AI-12685 and AI-TI-13.

² Postdoctoral trainee of the U. S. Public Health Service.