Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease.
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.
Paust
Silke
S
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, 44 Binney Street, SM 722, Boston, MA 02115, USA.
Lu
Linrong
L
McCarty
Nami
N
Cantor
Harvey
H
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000517:prevention & control*; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000276:immunology; D066298:In Vitro Techniques; D008231:Lymphopenia / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology*; D019282:Wasting Syndrome / Q000276:immunology
D018122:B7-1 Antigen; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2