SELECTIVE IMMUNOMODULATION BY THE AUTOIMMUNITY-INDUCING XENOBIOTICS STREPTOZOTOCIN AND HGCL2

Exposure to certain drugs and environmental chemicals can provoke the onset of autoimmune disease in susceptible individuals by releasing (s elf) epitopes for which tolerance has not been established, while simu ltaneously providing the necessary adjuvant activity. The resulting re sponse type is influenced by the genotype of exposed individuals and r elates to susceptibility to the adverse immune effects of the chemical s. Here, we assessed the modulatory role of the chemical compounds the mselves. A single injection of streptozotocin (STZ) increased the numb er of CD8(+) cells, macrophages, apoptotic cells, and IFN-gamma-produc ing T helper and T cytotoxic cells, whereas the number of CD4(+) cells and B cells was reduced in the draining lymph node. Coinjection with the reporter antigen TNP-OVA resulted in primary and secondary product ion of TNP-specific antibodies that were predominantly of IgG2a and Ig G2b isotype, whereas STZ did not enhance priming for delayed-type hype rsensitivity (DTH) responses to TNP-OVA. Injection of HgCl2 on the oth er hand, reduced the number of IFN-gamma-producing cells, induced accu mulation of B cells and CD4(+) and CD8(+) T cells, enhanced IgG1 and I gE production to TNP-OVA, and primed for secondary IgG1 and IgE produc tion as well as for DTH reactions. Together these results indicate tha t a single injection of STZ stimulates type-1 responses, whereas HgCl2 enhanced mixed type-1 and -2 responses in BALB/c mice. These response types match the (auto)immune effects elicited to unknown (auto)antige ns following multiple injections of these chemicals.