| Summary: | Brown Norway (BN) rats treated with mercuric chloride (HgCh) develop an auto immune syndrome characterized by the production of a variety of IgG autoantibodies, a marked increase in total serum IgE concentration and vasculitis. These features have some similarities to the Churg-Strauss syndrome in humans. The increase in IgE concentration is associated with increased interleukin-4 (IL-4), thus suggesting the involvement of the Th2 subset of CD4+ T cells. However, direct evidence of CD4+ Th2 cell involvement in this syndrome in the rat is lacking, as a cell surface marker of rat CD4+ Th2 cells has not been found to date. ST2L, a member of the IL-IR gene family has been reported as a stable selective marker of CD4+ Th2 cells in mice and has been proposed as a marker of Th2 cells. Equivalent data of the rat homologue, Fit-I, on rat CD4+ Th2 cells is not currently available. A short 20-amino acid sequence of Fit-l peptide was used to generate a monoclonal antibody against Fit-I. Characterization of the anti-Fit-l monoclonal antibody showed that the IgM antibody generated mainly binds to a population of cells eo-expressing CD45RA, a small sub-population of CD4+ in BN rats. Fit-l expression on CD8+ T cells was not clear. A small comparative study using anti-mouse ST2 polyclonal antibody also showed predominant expression of STL on rat CD45RA + cells and a small subpopulation of CD4+ and CD8+ T cells. The comparative pattern of ST2L and Fit-l expression observed endorses the notion that ST2L and Fit-l as homolgoues. However; the phenotype of rat cells expressing ST2L did not mirror the findings in mice i.e., ST2L expression on CD4+ Th2 cells. In vivo administration of the monoclonal antibody was found to selectively suppress serum levels of IgE antibody in HgCh-treated BN rats. An ELISpot assay was used to demonstrate IL-4 production at the protein level in HgCh-treated rats and the reactivity of anti-Fit-l mAb against IL-4-producing cells in vitro through a complement-dependent cytotoxic mechanism. The results suggest that there is some evidence that cells expressing Fit-l protein and secrete IL-4 may have a role in HgCh-induced IgE in particular and pathogenesis of HgCh-induced auto immune syndrome in BN rats in general, although further work is required to fully characterize the phenotype and cytokine profile of CD45RA+ Fit-l+ CD4+ Fit-l+ T cells. In conclusion, the monoclonal antibody raised against Fit-l is unlikely to be of use as a selective marker of CD4+ Th2 cells but preliminary evidence indicates that in vivo administration of anti-Fit-l mAb may possibly prevent IL-33 binding with ILIRLI on CD45RA+ Fit-l+, CD4+ Fit-l+ T cells and IL-4 producing cells thus blocking signalling cascade which in turn selectively inhibits HgCh-induced IgE antibody production. Perhaps further studies in the future will reveal the role of IL-33/Fit-1 complexin the pathogenesis of HgCh-induced autoimmune syndrome in BN rats.
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