Specific immunity to streptozocin. Cellular requirements for induction of lymphoproliferation.
The mechanism(s) of the immunological reactions involved in the pathogenesis of hyperglycemia induced by multiple intraperitoneal injections of subdiabetogenic doses of streptozocin (STZ) in mice remains to be elucidated. We found that STZ can act as a hapten in vivo by using the popliteal lymph node (PLN) assay. With this assay a direct toxic effect of STZ on the pancreatic beta-cells was dissociated from the effects exerted on the immune system. Subcutaneous injections of STZ induced immune reactivity in the draining PLN as determined by increase in weight, cell number, and [3H]thymidine incorporation. T-lymphocytes were required to induce the PLN response to STZ, because athymic nu/nu mice completely failed to respond to STZ, in contrast to their euthymic +/nu counterparts (P less than .001). The STZ-induced PLN response was sex independent and unaffected by prior subcutaneous injections of 3-O-methylglucose known to protect pancreatic beta-cells against STZ. STZ-primed mice exhibited an accelerated and enhanced STZ-specific secondary PLN response on challenge with subimmunogenic doses of STZ. In adoptive transfer experiments, STZ-sensitized splenic lymphocytes enriched for T-lymphocytes induced an STZ-specific significant (P less than .005) PLN enlargement provided the syngeneic recipients had been pretreated with subimmunogenic doses of STZ. Presumably, such STZ-specific immune reactions enhance a subtoxic effect of STZ on the pancreatic beta-cells.
D019325:3-O-Methylglucose; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000473:pathology; D007116:Immunization, Passive; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology; D007700:Kinetics; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008757:Methylglucosides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D013154:Spleen / Q000276:immunology / Q000637:transplantation; D013311:Streptozocin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D013936:Thymidine / Q000378:metabolism
D008757:Methylglucosides; D019325:3-O-Methylglucose; D013311:Streptozocin; D013936:Thymidine