Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease
Abstract
Although there is considerable evidence that a subpopulation of regulatory CD4+CD25+ T cells can suppress the response of autoreactive T cells, the underlying molecular mechanism is not understood. We find that transmission of a suppressive signal by CD4CD25+ regulatory cells requires engagement of the B7 molecule expressed on target T cells. The response of T cells from B7-deficient mice is resistant to suppression in vitro, and these cells provoke a lethal wasting disease in lymphopenic mice despite the presence of regulatory T cells. Susceptibility of B7-deficient cells to suppression is restored by lentiviral-based expression of full-length, but not truncated, B7 lacking a transmembrane/cytoplasmic domain. Because expression of these B7 truncation mutants restores CD28-dependent costimulatory activity, these findings that indicate B7-based transmission of suppressive activity suggest new approaches to modifying autoimmune responses.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- July 2004
- DOI:
- 10.1073/pnas.0403342101
- Bibcode:
- 2004PNAS..10110398P
- Keywords:
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- IMMUNOLOGY