Detection in vitro of cellular hypersensitivity to drugs.
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Biomedical subjects
Publications and source records attributed to J R David.
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Suppression of delayed hypersensitivity in vivo is correlated in vitro with the absence of macrophage migration inhibition in the presence of the antigen used to induce partial tolerance. The suppression of delayed hypersensitivity is antigen-specific in vivo as well as in vitro. The lymphocytes, and not the macrophages, are the cells involved in the induction of tolerance in terms of delayed hypersensitivity which is characterized by an absence of migratory factor activity.
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Lymph node lymphocytes obtained from guinea pigs exhibiting delayed hypersensitivity are stimulated in vitro by specific antigen to produce a soluble factor that is chemotactic in vitro for mononuclear macrophages. The material is nondialyzable, relatively heat stable, and elutes from Sephadex G-100 in the fraction containing molecules smaller than immunoglobulins.
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The immunochemical specificity of antigen-induced inhibition of peritoneal exudate cell migration was studied in animals sensitized to chemically defined alpha,DNP(Lys)(18) peptides. It was shown that sensitized peritoneal exudate cells could discriminate between various DNP-oligolysines. Only immunogenic members of the homologous series of alpha,DNP-L-lysines equal to or larger in size than the heptamer inhibited the migration of specifically sensitized peritoneal exudate cells. In contrast, nonimmunogenic alpha,DNP-L-lysines, a D-lysine containing stereoisomer of alpha,DNP L(Lys)(9) (alpha,DNP-L(4)DL(4)) and (Lys)(9)epsilon, DNP were not inhibitory to the migration of peritoneal exudate cells derived from animals immunized to alpha,DNP(Lys)(18). The exquisite specificity of the in vitro reaction of sensitized cells with antigen contrasts with the previously observed in vivo or in vitro specificity of anti-alpha,-DNP(Lys)(n) antibody, but parallels the specificity of the in vivo delayed or anamnestic response. These results suggest the presence of a still undefined but highly specific binding site, which functions as the cellular receptor for antigen on the sensitized lymphoid cell or on some "processing" cell.
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