Suppression and contrasuppression in athymic nude mice: nude mice produce the antigen-specific component of a T suppressor factor that inhibits the late 24-hr phase of DTH but do not generate suppression nor contrasuppression of the early initiating phase of DTH.
Previous studies demonstrated that the initiation of murine delayed-type hypersensitivity (DTH), as exemplified by contact sensitivity induced by picryl chloride (PCI) or oxazolone (OX), is due to antigen-specific, T cell-derived, DTH-initiating factors called, respectively, PCl-F and OX-F. These factors participate in the extravascular recruitment of CD4+, Th-1, DTH effector T cells in the elicitation of DTH. Related factors also participate, together with nonantigen binding factors derived from CD8+ T cells, to constitute an antigen-specific T cell-derived suppressor factor (TsF) that can down regulate the ability of Th-1 effector T cells to mediate DTH. Since it was shown recently that athymic nude mice can make antigen-specific, DTH-initiating T cell factors, the current study tested whether nude mice also could produce the antigen-specific component of the TsF that suppresses DTH effector T cells. We found that antigen-specific factors from nu/nu mice could complement the nonantigen-binding subfactor produced in normal mice to constitute the whole antigen-specific TsF. Additional studies showed that the successful adoptive cell transfer of DTH-initiating T cell activity from nude mice into normal mice required cyclophosphamide treatment of the recipient. In contrast, transfer of DTH-initiating cell activity from nu/+ mice did not require cyclophosphamide treatment of the recipients. We hypothesized that nude mice lacked contrasuppressor cells. Although nude mice were able to manifest the early, initiating phase of DTH, we found that there was no suppression of early DTH-initiating T cells in nude mice, compared to nu/+. Therefore the production of DTH-initiating T cell factor could be boosted in nude mice. The ability to boost DTH-initiating cells in nude mice should facilitate the development of cell lines and clones with the ability to initiate DTH.
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
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Herzog
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Ptak
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Askenase
D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000276:immunology; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D008819:Mice, Nude / Q000276:immunology*; D010081:Oxazolone / Q000276:immunology / Q000494:pharmacology; D010853:Picryl Chloride / Q000276:immunology / Q000494:pharmacology; D013491:Suppressor Factors, Immunologic / Q000494:pharmacology / Q000502:physiology; D013997:Time Factors
D000939:Epitopes; D013491:Suppressor Factors, Immunologic; D010081:Oxazolone; D003520:Cyclophosphamide; D010853:Picryl Chloride