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Selective immunomodulation by the autoimmunity-inducing xenobiotics streptozotocin and HgCl2
Abstract:
Exposure to certain drugs and environmental chemicals can provoke the onset of autoimmune disease in susceptible individuals by releasing (self) epitopes for which tolerance has not been established, while simultaneously providing the necessary adjuvant activity. The resulting response type is influenced by the genotype of exposed individuals and relates to susceptibility to the adverse immune effects of the chemicals. Here, we assessed the modulatory role of the chemical compounds themselves. A single injection of streptozotocin (STZ) increased the number of CD8+ cells, macrophages, apoptotic cells, and IFN-gamma-producing 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 production of TNP-specific antibodies that were predominantly of IgG2a and IgG2b isotype, whereas STZ did not enhance priming for delayed-type hypersensitivity (DTH) responses to TNP-OVA. Injection of HgCl2 on the other hand, reduced the number of IFN-gamma-producing cells, induced accumulation of B cells and CD4+ and CD8+ T cells, enhanced IgG1 and IgE production to TNP-OVA, and primed for secondary IgG1 and IgE production as well as for DTH reactions. Together these results indicate that 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)antigens following multiple injections of these chemicals.
Insights
Certain drugs like streptozotocin (STZ) and mercury chloride (HgCl2) can trigger autoimmune diseases by altering immune responses. STZ promotes type-1 immunity, while HgCl2 induces mixed type-1 and type-2 immune responses in mice.
Area of Science:
- Immunology
- Toxicology
- Autoimmunity
Background:
- Environmental chemicals and drugs can induce autoimmune diseases in susceptible individuals.
- Chemicals can release self-epitopes and act as adjuvants, initiating immune responses.
- Individual genetic makeup influences susceptibility to chemical-induced adverse immune effects.
Purpose of the Study:
- To investigate the modulatory role of specific chemical compounds on immune responses.
- To compare the immune effects of streptozotocin (STZ) and mercury chloride (HgCl2) in BALB/c mice.
- To determine the type of immune responses (e.g., type-1, type-2) elicited by STZ and HgCl2.
Main Methods:
- BALB/c mice were injected with STZ or HgCl2, alone or with the reporter antigen TNP-OVA.
- Flow cytometry was used to analyze immune cell populations (CD4+, CD8+, macrophages, B cells) in draining lymph nodes.
- IFN-gamma production by T helper and T cytotoxic cells was measured.
- Antibody production (IgG2a, IgG2b, IgG1, IgE) specific to TNP-OVA was assessed.
- Delayed-type hypersensitivity (DTH) responses to TNP-OVA were evaluated.
Main Results:
- STZ injection increased CD8+ cells, macrophages, apoptotic cells, and IFN-gamma-producing cells, while decreasing CD4+ and B cells.
- STZ promoted TNP-specific IgG2a and IgG2b antibody production but did not enhance DTH responses.
- HgCl2 injection reduced IFN-gamma-producing cells and increased B cells, CD4+, and CD8+ T cells.
- HgCl2 enhanced TNP-specific IgG1 and IgE production and primed for DTH reactions.
Conclusions:
- STZ predominantly stimulates type-1 immune responses.
- HgCl2 enhances mixed type-1 and type-2 immune responses, including DTH.
- The distinct immune profiles induced by STZ and HgCl2 may explain their differential roles in chemical-induced autoimmunity.