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.