Neonatal induction of tolerance to T(h)2-mediated autoimmunity in rats

Brown-Norway (BN) rats are highly susceptible to drug-induced immune dysreg ulations and when injected with mercuric chloride (HgCl2) or sodium aurothi opropanolsulfonate (ATPS), they develop a syndrome characterized by a polyc lonal B cell activation depending upon CD4(+) T(h)2 cells that recognize se lf-MHC class II molecules. Since peripheral tolerance of Th2 cells might be crucial in the prevention of immunological manifestations such as allergy, establishing conditions for inducing tolerance to HgCl2- or ATPS-mediated immune manifestations appeared to be of large interest. We report here that BN rats neonatally injected with HgCl2: (i) do not develop the mercury dis ease, (ii) remain resistant to HgCl2-induced autoimmunity at 8 weeks of age and later, provided they are regularly exposed to HgCl2, (iii) are still s usceptible to ATPS-induced immune manifestations, and (iv) exhibit spleen c ells that adoptively transfer tolerance to HgCl2-induced autoimmunity in na ive, slightly irradiated, syngeneic recipients. These findings demonstrate that dominant specific tolerance can be neonatally induced using a chemical otherwise responsible for T(h)2-mediated autoimmunity.