Ocular immune privilege promoted by the presentation of peptide on tolerogenic B cells in the spleen. II. Evidence for presentation by Qa-1

Ocular immune privilege promoted by the presentation of peptide on tolerogenic B cells in the spleen. II. Evidence for presentation by Qa-1
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DOI:
10.4049/jimmunol.166.1.26
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发表时间:
2001-01-01
影响因子:
4.4
通讯作者:
Niederkorn, JY
Niederkorn, JY
中科院分区:
医学2区
文献类型:
--
作者:
D'Orazio, TJ;Mayhew, E;Niederkorn, JY

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眼免疫赦免是眼睛的几个独特特征的结果,包括对眼前房中遇到的Ag的Th 1免疫应答的系统性下调-一种称为前房相关免疫偏离(ACAID)的现象。ACAID的诱导需要三种细胞群的参与:眼ACAID APC、脾B细胞和脾T细胞。由于B细胞在其他系统中参与致耐受性抗原呈递,我们假设B细胞负责ACAID中调节性T细胞的诱导。这项研究的中心假设是APC从眼睛迁移到脾脏,在那里它们释放抗原肽(OVA),这些抗原肽被脾脏B细胞捕获并呈递给T细胞。体外和体内研究的组合表明,脾B细胞,在体外与ACAID APC孵育,能够诱导ACAID时,转移到幼稚小鼠。ACAID的诱导需要β 2-微球蛋白在B细胞和ACAID APC上的正常表达,而不是在T抑制细胞上。此外,ACAID调节细胞的诱导需要TL/Qa区的B细胞和调节性T细胞之间的组织相容性。结果表明:1)B细胞是诱导ACAID所必需的; 2)ACAID B细胞不直接抑制迟发型超敏反应的表达; 3)ACAID B细胞诱导Ag特异性调节性T细胞需要TL/Qa区的组织相容性。
Ocular immune privilege is the result of several unique features of the eye, including the systemic down-regulation of Th1 immune responses to Ags encountered in the anterior chamber of the eye-a phenomenon termed anterior chamber-associated immune deviation (ACAID), The induction of ACAID requires the participation of three cell populations: the ocular ACAID APC, the splenic B cell, and the splenic T cell. Because B cells have been implicated in tolerogenic Ag presentation in other systems, we hypothesized that B cells were responsible for the induction of regulatory T cells in ACAID. The central hypothesis for this study is that APC from the eye migrate to the spleen where they release antigenic peptides (OVA) that are captured and presented to T cells by splenic B cells. A combination of in vitro and in vivo studies demonstrated that splenic B cells, incubated with ACAID APC in vitro, were capable of inducing ACAID when transferred to naive mice. The induction of ACAID required the normal expression of beta (2)-microglobulin on both the B cell and ACAID APC, but not on the T suppressor cells. Moreover, the induction of ACAID regulatory cells required histocompatibility between the B cells and regulatory T cells at the TL/Qa region. The results indicate that: 1) B cells are necessary for the induction of ACAID; 2) ACAID B cells do not directly suppress the expression of delayed-type hypersensitivity; and 3) the induction of Ag-specific regulatory T cells by ACAID B cells requires histocompatibility at the TL/Qa region.