The induction of hapten‐specific T cell tolerance using hapten‐modified lymphoid membranes II. Relative roles of suppressor T cells and clone inhibition in the tolerant state

The cellular nature and specificity of suppressor cells and the mechanisms of tolerance to 2,4‐dinitrophenyl‐l‐fluorobenzene (DNFB) in mice was investigated. Mice tolerized with hapten‐modified self membrane, i.e. dinitrophenylated spleen cells (DNP‐SC), generated suppressor cells as shown by their ability to transfer unresponsiveness to normal animals. Such suppressor cells were specific for DNFB as they did not interfere with sensitization of normal animals with 2,4,6‐trinitro‐1‐chlorobenzene (picryl chloride). These suppressor cells were of the thymus‐derived lymphocyte (T cell) lineage as (a) their activity was abolished by treatment with anti‐Θ serum plus complement, and (b) these cells could not be raised in T cell‐deprived mice. Kinetic studies of the development of tolerance showed discrepancies between the rate of induction of unresponsiveness in the donor (“phenotypic” tolerance) and the ability to transfer tolerance. One day after receiving 5 × 10  7 DNP‐SC mice were phenotypically tolerant but could not serve as the donors of suppressor cells. 7 days after tolerization with DNP‐SC mice were still fully tolerant and also contained suppressor cells, which were no longer demonstrable 14 days after tolerization when mice were still phenotypically tolerant. The ability to transfer tolerance was eliminated by pretreatment with cyclophosphamide (Cy). We postulate that two independent mechanisms of tolerance occur after tolerization with DNP‐SC ‐ the rapid induction of clone inhibition and the slower, transient induction of suppressor T cells. Cy had no effect on clone inhibition but eliminated the precursors of suppressor T cells.