LYMPHOCYTE-ACTIVATION BY LIPOSOME-TRAPPED STREPTOZOTOCIN IN MURINE POPLITEAL LYMPH-NODE (PLN) TEST

The lymphoproliferative potential of liposome-trapped streptozotocin ( STZ) was compared to the effect of saline-dissolved STZ injected local ly into the foot pad of CD-1 mice. Popliteal lymph node (PLN) enlargem ent and early cell activation of lymphocyte subsets were monitored dur ing the onset of STZ-induced autoimmune-like reaction. Injection of th e optimal STZ dose, 0.5 mg/foot pad, markedly increased the absolute P LN cell number as well as specific T-helper (CD4(+)), T-suppressor/cyt otoxic (CD8(+)), and B-(Ig(+)) cell subsets stained with fluorescent m onoclonal antibodies. Furthermore, there was a marked increase in the number of large/activated CD4(+) and CD8(+) cells and subsets bearing specific markers of early activation. These included cells stained wit h fluorescein-conjugated monoclonal antibodies against interleukin-2 r eceptor (CD25(+)) and early activation marker (EAM(+)) (CD69(+)), and with fluorescein-conjugated peanut agglutinin (PNA(+)). Surprisingly, the injection of liposome-trapped STZ, at a 1/10 of the optimal dose o nly, induced a marked PLN enlargement comparable to the effect of opti mal STZ dose. The effect of liposome-STZ could be dissociated from the non drug-containing MLV-related lymphocyte activation. The data sugge st several possible advantages from the introduction of chemicals by t he liposome route and the subsequent PLN test for chemical-induced aut oimmunity. Toxicological advantages could involve better control of ch emical exposure, controlled exposure to the water-insoluble substances , drastic reduction of xenobiotic dose, a stronger, clear PLN response and possible elimination or at least restriction of false-negative re sults, due to the liposome adjuvancity. Overall, application of liposo mes as an exposure route potentialized the STZ-induced early lymphocyt e activation.