LEW rats

HAuCl -induced T-cell activation resulted in early cytokine gene expression by lymphocytes from both BN and LEW rats since two to four hour incubation with the metal was sufficient to induce an increase in IL-4 and IFN-y mRNA. Nevertheless, the expression of IL-4 predominated in BN T-ceUs while the expression of IFN-y was favoured in LEW T-ceUs. The in vitro findings correlated quite well with the profile of cytokine expression in spleen cells of BN and LEW rats injected with HAuCl, which gave relevance to the in vitro data. The pronounced over-expression of IL-4 induced by gold in BN rats was probably related to the fact that BN rats mount preferential Th2 responses whatever the stimulus. It would be interesting to determine the frequency of IL-4 producing T-cells upon stimulation with gold and whether this phenotype concerns a peculiar T-cell subset. 

These differences between BN and LEW rats in susceptibility to metal-induced autoimmunity and nephropathy are associated with intrinsic differences in the immune system of these two strains. Indeed, from an immunological point of view, the balance between "type 1" (Thl/Tcl) and "type 2" (Th2/Tc2) cells is opposite in BN and LEW rats. BN rats are susceptible to "type 2"-mediated immunological disorders, to which the LEW strain is resistant. Conversely, "type l"-mediated organ-specific autoimmune disease are easily induced in LEW, but not in BN rats [155]. These immunological features depend on inherent properties of T lymphocytes. In vitro and in vivo studies have shown an inherent bias in T lymphocytes (CD4 and CDS) from BN and from LEW rats to produce respectively "type 2" (IL-4, IL-5, IL-13) and "type 1" (IFN-y cytokines [156-158]. The difference in susceptibility to metal-induced autoimmunity and nephropathy of BN and LEW strains provides a unique tool to study their genetic control. 

Savignac M, Badou A, DelmasC, Subra JF, De Cramer S, Paulet P, Cassar G, Druet P, Saoudi A, Pelletier L Gold is aTcell polyclonal activator in BN and LEW rats but favors IL-4 expression only in autoimmune prone BN rats. Eur. J. Immunol. 2001 31 2266-2276. 

Sapin C, Hirsch F, Delaporte J-P, et al. 1984. Polyclonal IgE increase after HgCl2 injections in BN and LEW rats A genetic analysis. Immunogenetics 20 227-236. 

The reasons why LEW rats are resistant to the development of gold-induced autoimmunity are unknown. However, two points are interesting 1) LEW MHC is permissive since Brown-Norway.IL rats, which have the same MHC as LEW rats and non MHC genes from the BN background, develop gold-induced disease as Brown-Norway rats and 2) administration of anti-IFN-y mAb render LEW rats partially susceptible to allochrysine-induced autoimmunity with the appearance of anti-laminin antibodies even if their titer is 5 times lower than in Brown-Norway rats [76]. This mild response could explain why IgG deposits are not found in the kidneys of LEW rats injected with allochrysine and anti-IFN-Y antibodies. 

Resistance of LEW rats to mercury-induced autoimmunity is due neither to CD8+ suppressor cells since treatment with an anti-CD8 mAb does... 

Pelletier L, Pasquier R, Rossert J, Druet P (1987b) HgCl2 induces non specific immunosuppression in LEW rats. Eur J Immnol 17 49-54... 

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