B7H costimulates clonal expansion of, and cognate destruction of tumor cells by, CD8+ T lymphocytes in vivo
B7H costimulates clonal expansion of, and cognate destruction of tumor cells by, CD8+ T lymphocytes in vivo
复制标题
DOI：
10.1084/jem.194.9.1339
复制
发表时间：
2001-11-05
影响因子：
15.3
通讯作者：
Liu, Y
中科院分区：
文献类型：
--
作者：
Liu, XL;Bai, XF;Liu, Y
B7 H/B7 RP（以下简称B7 H）是B7家族共刺激分子的新成员，与诱导型共刺激分子（ICOS）相互作用。其对CD 8 T细胞的功能尚未报道。我们在这里报告，表达B7 H的肿瘤细胞降低致瘤性和诱导免疫随后的挑战与亲本肿瘤细胞。免疫保护与针对P1 A（J558肿瘤中表达的主要肿瘤抗原）的所有增强的细胞毒性T淋巴细胞（CTL）应答相关。为了了解免疫保护的机制，我们将肿瘤抗原P1 A特异性转基因T细胞过继转移到携带P1 A表达肿瘤的小鼠中。我们发现，虽然转基因T细胞在携带B7 H（+）肿瘤的小鼠中分裂更快，但B7 H诱导的P1 CTL的最佳克隆扩增需要B7-1和B7-2对内源性宿主抗原呈递细胞（APC）的共刺激。有趣的是，当B7 H（+）和B7 H（-）肿瘤共注射时，P1 CTL选择性地消除B7 H（+）肿瘤细胞。此外，B7 H表达的肿瘤细胞使它们在体内对CTL的破坏高度敏感，即使CTL被施用到具有大的较小负荷的小鼠中。在P1 CTL处理的小鼠中复发的肿瘤失去了转染的B7 H和/或H-2L（d），即呈递P1 A肽的I类分子。综上所述，我们的研究结果表明，B7 H共刺激克隆扩增，并在体内同源破坏CD 8（+）T淋巴细胞。
B7H/B7RP (hereby called B7H) is a new member of the B7 family of costimulatory molecules and interacts with inducible costimulatory molecule (ICOS). Its function for CD8 T cells has not been reported. We report here that expression of B7H on the tumor cells reduced tumorigenicity and induced immunity to subsequent challenge with parental tumor cells. The immune protection correlates with all enhanced cytotoxic T lymphocyte (CTL) response against P1A, the major tumor antigen expressed in the J558 tumor. To understand the mechanism of immune protection, we adoptively transferred transgenic T cells specific for tumor antigen P1A into mice that bore P1A-expressing tumors. We found that while the transgenic T cells divided faster in mice bearing the B7H(+) tumors, optimal B7H-induced clonal expansion of P1CTL required costimulation by B7-1 and B7-2 oil the endogenous host antigen-presenting cells (APCs). Interestingly, when B7H(+) and B7H(-) tumors were coinjected, P1CTL selectively eliminated the B7H(+) tumor cells. Moreover, B7H expressed oil the tumor cells made them highly susceptible to destruction by CTL in vivo, even if the CTL was administrated into mice with large minor burdens. Tumors that recurred in the P1CTL-treated mice lost transfected B7H and/or H-2L(d), the class I molecule that presents the P1A peptide. Taken together, our results reveal that B7H costimulates clonal expansion of, and cognate destruction by CD8(+) T lymphocytes in vivo.