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PNAS 101 (28): 10398-10403

Copyright © 2004 by the National Academy of Sciences.

IMMUNOLOGY

Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease

Silke Paust, Linrong Lu, Nami McCarty, and Harvey Cantor *

Department of Cancer Immunology and AIDS, Dana–Farber Cancer Institute, Department of Pathology, Harvard Medical School, 44 Binney Street, SM 722, Boston, MA 02115

Contributed by Harvey Cantor, May 24, 2004

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.

Abbreviations: T-reg, CD4+CD25+ regulatory T cell; FACS, fluorescence-activated cell sorter; CTLA-4, cytotoxic T lymphocyte-associated antigen 4; GPI, glycosylphosphatidylinositol; wt, wild type; PE, phycoerythrin; Th, T helper; RAG-2, recombination activation gene 2; BM, bone marrow.

* To whom correspondence should be addressed. E-mail: harvey_cantor{at}dfci.harvard.edu.

© 2004 by The National Academy of Sciences of the USA

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