- March 21, 2014 at 2:25 am #117151
dvjorgeParticipantTopics: 283Replies: 1368
In vivo the environmental pollutants lead and mercury induce oligoclonal T cell responses skewed toward type-2 reactivities.
Heo Y1, Lee WT, Lawrence DA.
An oligoclonal utilization of Vbetas has been reported for pathogenesis of several autoimmune diseases, anti-tumorigenic activity, and superantigen-regulation of thymic T cell development. Altered ratios of Th1 and Th2 cells also are observed in immunodysregulations, leading to impaired cell-mediated immunity with an increased incidence of infectious disease or cancer and/or aberrant immunity that could culminate with an autoimmune disease. Lead (Pb) and mercury (Hg) are known pollutants with immunodisrupting activities; Hg is known to cause autoimmune glomerulonephritis. Both metals are known to suppress host resistance to pathogens. To further evaluate the manner by which these metals cause in vivo immunomodulation, their in vivo effects on Vbeta expression were evaluated along with the Th1 and Th2 frequency. Exposure of BALB/c mice to PbCl2 or HgCl2 induced an oligoclonal response with increases of Vbeta 5+, Vbeta 7+, and Vbeta 13+ CD4+ splenic, but not thymic, T cells. A significantly skewed frequency of Pb-induced splenic Th2 cells expressing Vbeta 7 or Vbeta 13 over Th1 cells was determined by limiting dilution analysis, but this Th2 predominance was not observed with CD4+ T cells expressing Vbeta 8. DO11.10 transgenic mouse exposed to Pb and antigen also demonstrated a skewed type-2 response evidenced by significantly increased IgE levels, lowered IFN-gamma levels, and increased IgG1 and lowered IgG2a anti-OVA levels. Even in the absence of specific T cell responses to a Pb-induced antigen, due to the restricted T cell specificity in the transgenic mouse model, Pb still was able to skew the response toward type-2 reactivity. However, this skewing occurred only in the presence of antigen. Therefore, the Pb-induced oligoclonal T cell response in BALB/c mice which must be initiated by self-antigens and was predominately type-2 may be responsible for autoantibody production and the detrimental health effects associated with Pb exposure.
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