NONRESPONSIVENESS TO MERCURY-INDUCED AUTOIMMUNITY IN RESISTANT DBA 2 MICE IS NOT DUE TO IMMUNOSUPPRESSION OR BIASED TH1-TYPE RESPONSE/

Mercury can induce systemic autoimmunity in susceptible mouse strains characterized by a T-cell-dependent polyclonal B-cell activation, incr eased serum levels of IgG1 and IgE antibodies, production of autoantib odies, and the formation of immune complexes in the kidneys. However, certain resistant mouse strains do not show any of the autoimmune mani festations after mercury injection. Th1/Th2 dichotomy has been propose d to be responsible for resistance and susceptibility, respectively. I mmunosuppression has also been suggested in resistant animals after me rcury injection. To test whether immunosuppression or a biased Th1-typ e response was induced by mercury in resistant DBA/2 mice, we injected DBA/2 mice with mercury for 1 or 3 weeks and then immunized the mice with horse red blood cells (HRBCs) to study whether the subsequent hum oral response to HRBCs was inhibited or skewed to the production of an tibodies of IgG2a isotype switched by Th1-type cytokines. We found tha t there was no reduction of the number of splenic antibody-producing c ells in the subsequent response to HRBCs compared with saline-treated mice. By haemagglutination tests, the titers of HRBC-specific antibodi es were the same after HRBCs injection in both mercury- and saline-tre ated DBA/2 mice. There was no increase in total serum IgG2a antibody. Sera of both mercury- and saline-treated mice immunized with HRBCs sho wed high titres of specific IgM, IgG1 and IgG2a anti-HRBCs antibodies. Surprisingly, 3-week treatment with mercury induced a reduction in th e titres of specific IgG2a anti-HRBCs antibodies in DBA/2 mice after i mmunization with HRBCs. Our results demonstrated that mercury did not induce a general immunosuppression or a biased Th1-type immune respons e in resistant DBA/2 mice. The nonresponsiveness in mice resistant to mercury-induced autoimmunity must be due to some other unknown mechani sm(s).