1. Sponsor Organization: NIH/NIEHS

2. Project Title: 03230-09 IMMUNE EFFECTS OF METALS--MERCURY-INDUCED AUTOIMMUNE DISEASE

3. Project Focus:

• Project Primary Focus: Human Health Effects
• Project Secondary Focus:

4. Description:

The administration of HgCl2 to Brown Norway (BN) rats produces an excellent animal model for studying xenobiotic-induced autoimmunity. Studies from our laboratory have shown that mercury-treated BN rats experience a decrease in peripheral RT6+ T lymphocytes, a change that precedes the appearance of circulating autoantibodies to renal antigens (e.g., laminin) and membranous glomerulonephritis. In contrast, Lewis (LEW) as well as congenic rats (between LEW and BN) are resistant to these effects of HgCl2, even when experimentally depleted of RT6+ T cells. Recently, we have observed that chimeric rats obtained by adoptive transfer of BN lymphocytes into gamma-irradiated LEW.IN congenic rats (BN-> LEW.IN chimeras) are susceptible to the autoimmune effects of mercury and experience a significant decrease in peripheral RT6.2+ T lymphocytes. On the basis of these observations we have suggested the hypothesis that mercury alters the delicate balance between T cells with suppressor (RT6.2+) and helper activities. that normally exists within the cellular (possibly cytokine-mediated) immunoregulatory network. We propose to continue the study of this hypothesis with the following Specific Aims: 1. Dissect the role of RT6.2+ T lymphocytes (and their subsets) In BN-> LEW.1N chimeras treated with HgCI2. We propose to perform adoptive transfers of purified RT6.2+T cells (or their fractionated subsets) to functionally identify their immunoregulatory activities. 2. Confirm the immunoregulatory properties of RT6.2+ T lymphocytes by their adoptive transfer Into BN rats prior to or during HgCl2 treatment.

5. References:

6. Inventory Category:

• Primary: Models
• Secondary:

7. Inventory Subcategory:

• Primary: Basic Research
• Secondary:

8. Keywords for Experimental System/Species:

• Species:
  • Mammal
  • Rodents
  • Rat
• Study Type:
  • Laboratory Study
• Fate and Transport:

9. Keywords for Experimental Endpoints:

• Health Effect:
  • Immunology
  • Molecular
• Hormonal Measures:
• Level Of Study:
• Chemistry Metabolism:
• Life Stage:
• Risk Assessment:

10. Chemical Agents:

• Mercury

11. Performing Institution:

• UNIVERSITY OF CONNECTICUT HEALTH CENTER

12. Contact:

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