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From the Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, and the Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20014
Abstract
Guinea pigs primed with 2,4-dinitrophenyl (DNP)-ovalbumin (OVA) will develop markedly enhanced secondary anti-DNP antibody responses to the heterologous conjugate DNP-bovine
globulin (BGG) provided that they have been supplementally immunized with appropriate amounts of BGG. This phenomenon reflects the enhancing influence of BGG-specific thymus-derived (T) lymphocytes on anti-DNP antibody production. The present studies demonstrate that such enhancing T cell influences can be abolished by the following manipulations: 1) simultaneous supplemental immunization with two unrelated proteins such as BGG and keyhole limpet hemocyanin (KLH) or glucose oxidase (GO) significantly diminished the secondary anti-DNP response upon challenge with a DNP-conjugate of one of the carriers employed; 2) the intraperitoneal injection of soluble BGG, in the appropriate dose range, 1 day before secondary DNP-BGG challenge completely abolishes the anti-DNP response regardless of whether BGG alone or BGG together with KLH had been used in the supplemental immunization; 3) a challenge with soluble KLH 1 day before secondary challenge with DNP-BGG inhibits the anti-DNP response provided KLH had been administered simultaneously with BGG in the supplemental immunization. The failure to observe similar suppression when KLH was replaced by a copolymer of d-glutamic acid and d-lysine (D-GL) which is nonimmunogenic for T cells indicates that this suppression is a reflection of a T cell-mediated influence.
We have interpreted these observations to indicate the production of soluble inhibitory mediators in phenomena such as antigen-induced suppression ("antigenic competition") and, furthermore, that the elaboration of such mediators is most likely by T lymphocytes. Reasons for favoring the concept that enhancing or inhibitory influences on antibody production represent two ends of the spectrum of regulation exerted, perhaps, by the same T cell product are discussed.
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