The Journal of Experimental Medicine, Vol 137, 1494-1510,
Copyright © 1973 by The Rockefeller University Press
MECHANISMS IN THE SUPPRESSION OF DELAYED HYPERSENSITIVITY IN THE GUINEA PIG BY 6-MERCAPTOPURINE
S. Michael Phillips 1 and
Burton Zweiman 1
1 From the Immunology Laboratory, Cardiorenal Section, Department of Medicine, Peter Bent Brigham Hospital and Harvard Medical School, Boston, Massachusetts 02115, and Allergy and Immunology Section, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
The mechanism of suppression, of delayed hypersensitivity to tuberculoprotein by 6-mercaptopurine (6-MP) was studied in guinea pigs. Under the conditions of the protocol, suppression of tuberculin delayed skin test reactivity was not associated with a significantly altered end-organ response to mediators of permeability. No significant alteration of in vivo lymphoid activity, as measured by reconstitution studies, was found. In addition, lymphoid cells from 6-MP-treated animals reacted in a fashion similar to those of placebo-treated animals with respect to (a) antigen-induced lymphocyte proliferation, (b) antigen-induced liberation of macrophage inhibitory factor activity, (c) direct inhibition by antigen of peritoneal exudate cell migration.
Conversely, suppression was seen in levels of blood monocytes and in vitro function of macrophages from 6-MP-treated animals in several respects: (a) adherence to glass, (b) migratory rate, (c) phagocytic capacity. Therefore, it would appear that a ma]or mechanism of 6-MP-induced suppression of delayed hypersensitivity is through its action on effector cells.
Submitted on December 28, 1972