SELF-REACTIVE ANTICLASS-II T-HELPER TYPE-2 CELL-LINES DERIVED FROM GOLD SALT-INJECTED RATS TRIGGER B-CELL POLYCLONAL ACTIVATION AND TRANSFER AUTOIMMUNITY IN CD8-DEPLETED NORMAL SYNGENEIC RECIPIENTS

Brown Norway (BN) rats given gold salts develop an autoimmune syndrome with an immune complex-type glomerulonephritis in the context of a po lyclonal B cell activation that was suspected to be due to the emergen ce of anti-self major histocompatibility complex (MHC) class II T cell s. In the present study, six anti-self MHC class II T cell lines have been derived from six gold salt-treated rats by repeated stimulations with normal syngeneic MHC class II-bearing cells. The T cell lines pro liferated in the presence of self MHC class II-positive B cell-enriche d or B cell-depleted cells and the proliferation was inhibited by prei ncubating stimulator cells with an anti-IA monoclonal antibody. The T cell lines produced interleukin (IL)-4 only or IL-4 and some interfero n (IFN)-gamma and could, therefore, be considered as T helper type 2 ( Th2) and Th0 cells, respectively. They triggered normal syngeneic B ce lls to produce in vitro IgE, anti-DNA, anti-laminin and anti-2,4-6-tri nitrophenol antibodies through, at least in part, cognate interactions . More interestingly, these lines when transferred into normal BN rats induced an autoimmune syndrome similar to or even more severe than th e one observed in the active gold model, provided the recipients were CD8 depleted. These manifestations included a dramatic increase in ser um IgE concentration and the production of anti-DNA and anti-laminin a ntibodies. In addition, all recipients displayed an autoimmune glomeru lonephritis due to anti-laminin antibodies, granular IgG deposits in t he interstitium, in the vessel walls and along the tubular basement me mbranes and a severe tubuloin-terstitial nephritis with marked mononuc lear cell infiltration. An anti-ovalbumin T cell line that produced IL -4 and low amounts of IFN-gamma was used as a control and did not indu ce autoimmunity. These results demonstrate for the first time the abil ity of autoreactive Th2 as well as Th0 cell lines to induce antibody-m ediated autoimmunity. They also show that CD8(+) cells play a crucial role in the control of such autoreactive cells. Finally, this work sug gests that Th2 cells could initiate cell-mediated reactions either dir ectly or indirectly.