Specific T Cell-Dependent, Antigen-Antibody Mediated Suppression of Macrophages: Abrogation by Nonspecifically Stimulated T Cells

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Abstract
The injection of hyperimmune antibody to leukemia L1210 into allogeneic mice before challenge with L1210 suppressed the ability of their peritoneal macrophages to take up L1210 cells in the presence of specific cytophilic antibody. This suppression has previously been shown to be thymus-dependent. Although the adoptive transfer of syngeneic normal thymocytes i.v. failed to overcome the suppression of macrophages, administration of an unrelated alloantigen, leukemia EL4, together with syngeneic thymocytes, did reverse suppression. The transfer of allogeneic thymocytes, without further antigen, also overcame suppression thereby enabling them to attach L1210 normally. Syngeneic peripheral (splenic) T cells with alloantigen, or allogeneic peripheral T cells, were somewhat less effective than thymocytes at reversal, and non-T cells were completely ineffective. Pretreatment of the donors of syngeneic thymocytes with unrelated alloantigen i.p. from a minimum of 4 hr to 14 days before transfer also restored functional competence to the macrophages. Nonspecific antigenic stimulation of a population of naïve thymocytes appears to prevent their recruitment as suppressor T cells, perhaps by changing the individual cell, by altering the cellular composition of the thymus gland, or by both. These data point up similarities between the “enhancement” phenomenon (immunosuppression caused by antibody and antigen) and “infectious immunologic tolerance,” in both of which T cells are intimately involved. The data also suggest that the macrophage may be a cellular site of specific immunologic unresponsiveness.

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