Role of CD8+ T cells in mercury-induced autoimmunity or immunosuppression in the rat.
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.
Pelletier
L
L
INSERM U28, Hôpital Broussais, Paris, France.
Rossert
J
J
Pasquier
R
R
Vial
M C
MC
Druet
P
P
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001323:Autoantibodies; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology*; D016827:CD8 Antigens; D004195:Disease Models, Animal; D005260:Female; D005921:Glomerulonephritis / Q000139:chemically induced / Q000276:immunology*; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride; D011507:Proteinuria / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D001323:Autoantibodies; D016827:CD8 Antigens; D007074:Immunoglobulin G; C051951:antiglomerular basement membrane antibody; D007073:Immunoglobulin E; D008627:Mercuric Chloride