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The Journal of Immunology, Vol 138, Issue 11 3675-3679, Copyright © 1987 by American Association of Immunologists

ARTICLES

Macrophage handling of a tolerogen and the role of IL 1 in tolerance induction in a helper T cell clone in vitro

JD Levich, AP Signorella, G Wittenberg and WO Weigle

The human gamma-globulin (HGG)-specific helper T cell clone AB.7.D7 can reconstitute the plaque-forming cell response of HGG-primed B cells. Tolerance induction at the level of T cell help results from exposure of the AB.7.D7 cells to 10 micrograms monomeric HGG. The monokine IL 1 was found to interfere with tolerance induction in AB.7.D7 cells in a dose-dependent manner. Furthermore, interference with tolerance induction was dependent upon the T cells being presented with IL 1 at the same time as monomeric HGG, the tolerogen. IL 1 and monomeric HGG could not be demonstrated to interact to make nontolerogenic soluble aggregates, however. It was found that monomeric HGG was unable to stimulate the production of either membrane or secreted IL 1 by splenic macrophages and in addition was not degraded by peritoneal exudate cells. Heat-aggregated HGG, which is highly antigenic and nontolerogenic, is a good stimulus for IL 1 production and is processed by macrophages into peptides of varying sizes. These data are consistent with the suggestion that a tolerogenic signal results from T cell recognition of a nondegraded antigen in the absence of a signal from IL 1. It is possible, however, that small amounts of processed antigen, undetectable by us, are involved.


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