Autoreactive T lymphocytes are pivotal in organ-specific autoimmune diseases and contribute substantially to tissue damage in diseases such as diabetes and rheumatoid arthritis. Immunotherapy can eliminate pathological cells but directing effective therapeutic T lymphocytes against autoreactive T cells has proved difficult. In November 11 Nature Biotechnology, Divya Jyothi and colleagues at St. Jude Children's Research Hospital, Memphis, USA, show that receptor-modified T cells (RMTC) can be directed against autoreactive T lymphocytes and can be uses to treat a model autoimmune disease (Nature Biotechnology, doi:10.1038/nbt758, November 11, 2002).

Jyothi et al. created RMTC by expressing a heterodimeric chimeric receptor that genetically links an autoantigenic peptide, its restricting MHC, and the signal transduction domain of the T-cell receptor ζ-chain. They observed that this change in receptor expression was able to redirect therapeutic T cells against cognate autoantigenspecific T cells. In addition, they showed that RMTC prevented and treated a model autoimmune disease — experimental allergic encephalomyelitis — even after epitope spreading had diversified the autoantigenic response.

"These results provide a model for the specific targeting of autoantigenic T cells in vivo. By manipulating the effector cell type, antigen presented, and signal transduced, it should be possible to design receptors and create optimized for specific therapeutic goals," conclude the authors.