In vivo the environmental pollutants lead and mercury induce oligoclonal T cell responses skewed toward type-2 reactivities

Heo, Y; Lee, WT; Lawrence, DA

HERO ID

73138

Reference Type

Journal Article

Year

1997

Language

English

PMID

9268502

HERO ID 73138
In Press No
Year 1997
Title In vivo the environmental pollutants lead and mercury induce oligoclonal T cell responses skewed toward type-2 reactivities
Authors Heo, Y; Lee, WT; Lawrence, DA
Journal Cellular Immunology
Volume 179
Issue 2
Page Numbers 185-195
Abstract An oligoclonal utilization of V"beta" 's 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 causein vivoimmunomodulation, theirin vivoeffects on V"beta" expression were evaluated along with the Th1 and Th2 frequency. Exposure of BALB/c mice to PbCl2or HgCl2induced an oligoclonal response with increases of V"beta" 5+, V"beta" 7+, and V"beta" 13+CD4+splenic, but not thymic, T cells. A significantly skewed frequency of Pb-induced splenic Th2 cells expressing V"beta" 7 or V"beta" 13 over Th1 cells was determined by limiting dilution analysis, but this Th2 predominance was not observed with CD4+T cells expressing V"beta" 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.
Doi 10.1006/cimm.1997.1160
Pmid 9268502
Wosid WOS:A1997XV90800010
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English