Role of CD8⁺ T Cells in Mercury‐Induced Autoimmunity or Immunosuppression in the Rat

Abstract

In Brown-Norway (BN) rats mercuric chloride induces an autoimmune disease characterized by an increase in serum IgE concentration, and by the production of anti-glomerular basement membrane antibodies responsible for a glomerulonephritis with a heavy proteinuria. (i) This disease results from a B-cell polyclonal activation probably due to frequent anti-class II T cells. (ii) The self limitation observed in this model is associated with both a decrease in the frequency of anti-class II T cells and the emergence of CD8+ T cells able to suppress these autoreactive T cells. (iii) In Lewis (LEW) rats which do not develop autoimmunity, HgCl2 provokes the appearance of non-antigen-specific CD8+ T cells responsible for a depression of T-cell functions. The aim of this work was to test the effect of treatment with an anti-CD8 monoclonal antibody (MoAb) in both BN and LEW rats. Anti-CD8 MoAb-treated rats were effectively depleted in CD8+ T cells. However, neither the induction nor regulation phases of mercury-induced autoimmunity were modified in BN rats. Mercury-induced immunosuppression in LEW rats was abrogated; however, depletion in CD8+ T cells did not allow the disease to occur in that strain. Finally, CD8 depletion induced in normal BN rats the appearance of rare anti-class II T cells showing that these cells are normally present in that strain but negatively controlled by suppressor T cells.

Mechanisms of T cell-induced glomerular injury in anti-glomeruler basement membrane (GBM) glomerulonephritis in rats

“…CD8 depletion also prevented macrophage influx and proteinuria, suggesting a pivotal role for CD8 cells as well as CD4 cells in inducing injury through macrophage recruitment in this model. A similar role for CD8 T cells has also been demonstrated in other disease models of autoimmunity, including experimental allergic encephalomyelitis (EAE) [36], in diabetic models in non-obese diabetic (NOD) mice [37][38][39] and in experimental models of mercuric chloride inducing nephritis in rats [40,41].…”

Anti-CD8 treatment reduces the severity of inflammatory arthritis, but not vasculitis, in mercuric chloride-induced autoimmunity

“…If this is the case it might be predicted that OX8 treatment would exacerbate the syndrome in HgCl 2 -treated naive animals. This has not been found and, instead, the titre of anti-GBM antibodies and the severity of proteinuria was suppressed in HgCl 2 + OX8-treated animals [10,11]. These observations contrast with the transfer experiments and suggest that in this situation CD8 + cells may have a proinflammatory effect in the initiation phase of the syndrome.…”

“…Other reports of OX8-treated BN rats have not demonstrated a significant difference in the initiation or autoregulation of the primary humoral response induced by HgCl 2 [10,11], even though an increase in CD8 + cells occurs in peripheral blood, joints and other tissues at the time of peak disease [4,12].…”

Effect of the thiol group on experimental gold‐induced autoimmunity

“…Indeed, this chemical induces a lymphoproliferation of CD4+ T cells and B cells, a hyperimmunoglobulinemia that preferentially affects IgE, and the production of various antibodies to self and non-self antigens (4) in BN rats. In addition, gold-induced autoimmunity shares many similarities with HgCI,-induced autoimmunity (lo), which is clearly a T cell-dependent disease (12).…”