Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 20 July 2004
Vol. 2004, Issue 242, p. tw258
[DOI: 10.1126/scisignal.2422004tw258]

EDITORS' CHOICE

IMMUNOLOGY Suppressing Autoimmune Responses Through B7

CD4+CD25+ regulatory T cells (Treg) play a key role in suppressing autoimmune activity. Their ability in vitro to inhibit the proliferation of other lymphocytes depends on direct contact; however, the underlying mechanisms are unclear. Noting that the B7 transmembrane proteins, which are expressed on antigen-presenting cells (APCs) and provide costimulatory signals to T cells, are also expressed on activated T cells, Paust et al. investigated their role in Treg-mediated suppression. Treg cells failed to suppress in vitro proliferation of activated CD4+CD25 T helper (Th) cells isolated from mice lacking B7 (B7-deficient Th), regardless of the presence of B7 on APCs. Proliferation of Th cells lacking B7-1 (CD80) or B7-2 (CD86) was partly resistant to Treg, whereas that of cells lacking both was fully resistant. Wild-type Th cells or B7-deficient Th cells transferred to RAG-2 (recombination activating gene-2-deficient) mice (which lack lymphocytes) promoted autoimmune gastritis and colitis. However, the mice that received B7-deficient Th cells also developed lethal wasting, and unlike mice that received wild-type Th cells, Treg did not suppress their autoimmune symptoms. In vitro susceptibility of B7-deficient Th to Treg suppression was restored by viral infection of the Th cells with B7-1. Full-length B7-1 or B7-2, but not mutants consisting of the B7-1 or B7-2 extracellular domains anchored with the glycosophosphatidylinositol (GPI) signal sequence (which retained costimulatory activity when expressed in APCs), conferred sensitivity to Treg suppression of B7-deficient Th cell proliferation after adoptive transfer to RAG-2 mice. Thus, B7 appears to mediate Treg suppression of Th cells, through outside-in signaling that requires the transmembrane or cytoplasmic domains.

S. Paust, L. Lu, N. McCarty, H. Cantor, Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Proc. Natl. Acad. Sci. U.S.A. 101, 10398-10403 (2004). [Abstract] [Full Text]

Citation: Suppressing Autoimmune Responses Through B7. Sci. STKE 2004, tw258 (2004).


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882