B7家族成员B7-H3优先下调1型辅助性T细胞介导的免疫反应。

The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses.

作者信息

Suh Woong-Kyung, Gajewska Beata U, Okada Hitoshi, Gronski Matthew A, Bertram Edward M, Dawicki Wojciech, Duncan Gordon S, Bukczynski Jacob, Plyte Suzanne, Elia Andrew, Wakeham Andrew, Itie Annick, Chung Stephen, Da Costa Joan, Arya Sudha, Horan Tom, Campbell Pauline, Gaida Kevin, Ohashi Pamela S, Watts Tania H, Yoshinaga Steven K, Bray Mark R, Jordana Manel, Mak Tak W

机构信息

Advanced Medical Discovery Institute, Ontario Cancer Institute, and Department of Medical Biophysics, University of Toronto, 620 University Avenue, Toronto, Ontario M5G 2C1, Canada.

出版信息

Nat Immunol. 2003 Sep;4(9):899-906. doi: 10.1038/ni967. Epub 2003 Aug 17.

DOI:10.1038/ni967

PMID:12925852

Abstract

We investigated the in vivo function of the B7 family member B7-H3 (also known as B7RP-2) by gene targeting. B7-H3 inhibited T cell proliferation mediated by antibody to T cell receptor or allogeneic antigen-presenting cells. B7-H3-deficient mice developed more severe airway inflammation than did wild-type mice in conditions in which T helper cells differentiated toward type 1 (T(H)1) rather than type 2 (T(H)2). B7-H3 expression was consistently enhanced by interferon-gamma but suppressed by interleukin 4 in dendritic cells. B7-H3-deficient mice developed experimental autoimmune encephalomyelitis several days earlier than their wild-type littermates, and accumulated higher concentrations of autoantibodies to DNA. Thus, B7-H3 is a negative regulator that preferentially affects T(H)1 responses.

摘要

我们通过基因靶向研究了B7家族成员B7-H3（也称为B7RP-2）的体内功能。B7-H3抑制由抗T细胞受体抗体或同种异体抗原呈递细胞介导的T细胞增殖。在T辅助细胞向1型（TH1）而非2型（TH2）分化的条件下，B7-H3缺陷小鼠比野生型小鼠发生更严重的气道炎症。在树突状细胞中，B7-H3的表达持续受到干扰素-γ的增强，但受到白细胞介素4的抑制。B7-H3缺陷小鼠比其野生型同窝小鼠早几天发生实验性自身免疫性脑脊髓炎，并积累了更高浓度的抗DNA自身抗体。因此，B7-H3是一种负调节因子，优先影响TH1反应。