Thymus Atrophy and Changes in Thymocyte Subpopulations of BN Rats with Mercury-Induced Renal Autoimmune Disease

Abstract

Administration of low doses of mercury induces autoantibodies to laminin and autoimmune glomerulonephropathy in BN, MAXX and DZB rats as well as in (BN × LEW)F₁ hybrids. LEW strain rats are resistant to these immunotoxic effects. Susceptible rats also show lymphoid hyperplasia in spleen and lymph nodes and severe thymic atrophy. It is still uncertain whether these mercury-induced changes have any role in the induction of autoimmune responses to laminin. In the present study, we have examined the effects of mercury on the thymus of susceptible and resistant rats. Histological analysis of thymuses from BN rats revealed extensive disorganization within 15 days following mercury treatment, with loss of demarcation between cortex and medulla. Numbers of thymus cells were significantly decreased in both BN and (BN × LEW)F₁ hybrid rats injected with HgCI₂. There was no apparent increase in apoptotic cells in the thymus of these animals. By flow cytometry we detected a relative and absolute loss of double-positive CD4⁺ CD8 ⁺thymocytes in BN (but not in LEW rats) within 15 days of mercury treatment. There was a corresponding increase in the relative proportion of single-positive (CD4⁺ or CD8 ⁺) and double-negative CD4⁻ CD8⁻ thymocytes in mercury-treated BN rats. Absolute increases in the number of CD4⁺ single-positive thymocytes were also observed. In contrast, mercury-treated LEW rats had no changes in thymus architecture or significant decreases in cell numbers. Since the thymus is important in both positive and negative selection of developing thymocytes, immunotoxic effects of mercury on its structure and thymocyte subpopulations may have multiple consequences. Alternatively, we suggest the hypothesis that autoimmunity (and in particular autoantibodies to laminin) may be responsible for the changes observed in the thymus.

Key Words:

• Apoptosis
• autoimmune disease
• cortical thymocytes
• flow cytometry
• HgCI₂
• mercury-induced renal autoimmunity
• stress
• thymic atrophy
• thymocyte subpopulations
• thymus
• xenobiotic-induced immunotoxicity