Neonatal induction and maintenance of tolerance to Th2-induced immune manifestations in rats.
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Biomedical subjects
Publications and source records attributed to J Fillion.
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Brown-Norway (BN) rats are highly susceptible to drug-induced immune dysregulations and when injected with mercuric chloride (HgCl(2)) or sodium aurothiopropanolsulfonate (ATPS), they develop a syndrome characterized by a polyclonal B cell activation depending upon CD4(+) T(h)2 cells that recognize self-MHC class II molecules. Since peripheral tolerance of T(h)2 cells might be crucial in the prevention of immunological manifestations such as allergy, establishing conditions for inducing tolerance to HgCl(2)- or ATPS-mediated immune manifestations appeared to be of large interest. We report here that BN rats neonatally injected with HgCl(2): (i) do not develop the mercury disease, (ii) remain resistant to HgCl(2)-induced autoimmunity at 8 weeks of age and later, provided they are regularly exposed to HgCl(2), (iii) are still susceptible to ATPS-induced immune manifestations, and (iv) exhibit spleen cells that adoptively transfer tolerance to HgCl(2)-induced autoimmunity in naive, 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.
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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.
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A method is described for the determination of 251 pesticide and degradation product residues in fruit and vegetable samples. Extraction of the sample with acetonitrile is followed by a salting-out step. Co-extractives are removed by passing a portion of the acetonitrile extract through an octadecyl (C18) solid-phase extraction cleanup cartridge and then, in a second cleanup, through a carbon cartridge coupled to an amino propyl cartridge. Determination is by gas chromatography with mass-selective detection in the selected-ion monitoring mode, and by liquid chromatography with post-column reaction and fluorescence detection for N-methyl carbamates. The method has been used for analysis of various fruits and vegetables, such as apple, banana, cabbage, carrot, cucumber, lettuce, orange, pear, pepper, and pineapple. Limits of detection range between 0.02 and 1.0 mg/kg for most compounds. Over 80% of the compounds have a limit of detection of < or = 0.04 mg/kg.