Ig-specific T cell receptor transgenic T cells are not deleted in the thymus and are functional in vivo

The mechanisms that induce T cell tolerance to circulating self-proteins are still controversial, and both the deletion and selection of autoreactive T cells have been observed in the thymus of transgenic mouse models. To address the question of the induction of tolerance to circulating self-constituents, a T cell receptor-transgenic mouse specific for the serum protein immunoglobulin (Ig) gamma and (IgG2a(b)) was generated. The choice of an allotype-specific T cell also allowed the generation of transgenic control mice not expressing the self-antigen. It was found that the transgenic T cells were not deleted in the thymus, did not become tolerant in the periphery, and regulated the function of gamma 2a(b)-positive B cells as shown by the lack of IgG2a(b) protein in the serum of the transgenic mice. In spite of this activity in vivo, the transgenic T cells did not proliferate in vitro in response to the allotype-specific peptide. Interestingly, antigen-specific T cell proliferation could be restored if the transgenic mice were previously challenged to induce IgG2a(b) responses. After this challenge, IgG2a(b) protein in the serum of the transgenic mice could be partially restored, although still remaining much lower than in control mice. In addition, there was a dramatic increase in serum IgE levels, suggesting that newly generated gamma 2a(b)-secreting B cells can be induced to switch to IgE in the presence of allotype-specific T cells. These results indicate that Ig-specific T cells may represent a late-acting form of T cell help for the regulation ofthe IgG2a-to-IgE class switch.