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Nonantibody mediated suppression of delayed hyper sensitivity to human gamma globulin in mice



Nonantibody mediated suppression of delayed hyper sensitivity to human gamma globulin in mice



Cellular Immunology 26(2): 228-241



Development of delayed hypersensitivity (DHS) to human .gamma.-globulin (HIgG) in mice was documented by histological analysis, by the kinetics of footpad swelling in animals exhibiting humoral or delayed responses, and by the failure of sera to transfer delayed reactions to normal, syngeneic recipients. Since cyclophosphamide (CY) treatment resulted in diminished humoral and augmented delayed reactions, this treatment was used as a tool to explore the nature of the regulatory mechanisms which affect expression of this type of cell-mediated immunity. To evaluate the effect which the presence or absence of antigen-specific cells might exert on expression of DHS, mice were subjected to experimental regimes which would result in lymphocyte proliferation or depletion, respectively. Cell proliferation was induced by injection of 80 .mu.g of aqueous antigen on day -4; this was followed by sensitization with HIgG-CFA (Freund's adjuvant) on day 0 and footpad challenge on day 13. These mice exhibited strong humoral reactivity; 3 of 6 died of anaphylaxis following footpad challenge, and the remaining 3 showed a diminished delayed response. Similarly treated mice that received 6 mg of CY 3 days after injection of aqueous antigen and, therefore, would have antigen-specific cells present, showed greatly diminished humoral reactivity due to B[bone marrow-derived]-cell depletion. They also exhibited a marked diminution in delayed responsiveness. A nonantibody-mediated, possibly cell-directed, regulatory influence is exerted on DHS where cell proliferation has occurred. The impact which the depletion of proliferating cells would exert on the expression of DHS was examined. Cell depletion was attempted by giving 1 injection of aqueous antigen (day 0) early in a regime of chronic CY administration (days -1 through +3); antigen-induced proliferating cells would be susceptible to CY and depleted under these conditions. Mice receiving aqueous antigen and CY have depressed humoral and markedly diminished delayed reactivity compared to animals that were injected with CY alone. The augmenting effect which CY exerts on DHS is abrogated by stimulation with aqueous antigen. CY apparently removes a regulatory cell population in the normal animal, thereby allowing enhanced expression of delayed responsiveness. Clearly, regulatory function cannot be attributed solely to humoral antibody production.

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Accession: 005991375

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PMID: 1086145


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