Evidence for heterogeneous TCR V beta repertoire expression in mercury-induced immune disorders in rats.
Administration of subtoxic doses of HgCl2 affects differentially the immune system depending on the strain of rats tested. Susceptible Brown-Norway (BN) rats exhibit a CD4+ T cell-dependent polyclonal activation of B cells; in contrast, Lewis (LEW) rats are resistant and develop an immunosuppression mediated by CD8+ T cells recruited by CD4+ T cells. The mechanisms by which mercury induces immune disorders are poorly understood. We were interested in analyzing the diversity and mercury-mediated changes of the TCR Vbeta repertoire in the BN and LEW strains of rats at different times of HgCl2 exposure. Our results obtained after analysis of lymph node T cells by RNase protection assay, flow cytometry or immunoscope assay (i) were not consistent with a superantigen-like stimulus since we observed neither a V beta-selective expansion nor deletion that would have been expected and (ii) showed that in BN rats, as well as in LEW rats, an increase in the number of T cells was associated with the heterogeneous TCR V beta repertoire, thus supporting a polyclonal T cell activation. However, in BN rats the total number of T cells increased very rapidly, whereas in LEW rats only CD8+ T cells accumulated.
Fillion
J
J
INSERM U430, Hôpital Broussais, Paris, France.
Baccala
R
R
Pannetier
C
C
Kuhn
J
J
Druet
P
P
Bellon
B
B
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000276:immunology* / Q000378:metabolism; D015704:CD4 Antigens / Q000737:chemistry; D016827:CD8 Antigens / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D007135:Immunoglobulin Variable Region / Q000145:classification; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D008628:Mercury / Q000009:adverse effects / Q000276:immunology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000145:classification / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D015704:CD4 Antigens; D016827:CD8 Antigens; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta; D008628:Mercury