Shen Linling, Barabino Stefano, Taylor Andrew W, Dana M Reza
Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA.
Arch Ophthalmol. 2007 Jul;125(7):908-15. doi: 10.1001/archopht.125.7.908.
To determine whether the ocular anterior segment (aqueous humor and cornea) actively inhibits dendritic cell (DC) maturation.
Dendritic cells were injected into syngeneic corneas or conjunctivae, and their surface major histocompatibility complex class II expression in response to the local milieu was assessed using confocal microscopy. Immature DCs were cocultured with corneal supernatant or with aqueous humor to evaluate their regulation of DC phenotypic and functional maturity.
In contrast to conjunctivally injected DCs, DCs injected into the cornea resisted up-regulation in expression of surface major histocompatibility complex class II. Corneal supernatant-treated and aqueous humor-treated DCs retained their immaturity, as reflected by high antigen uptake but low costimulatory molecule (CD80 and CD86) expression and poor T-cell stimulation. Anti-transforming growth factor beta(2) treatment of aqueous humor and of corneal supernatant led to complete and partial blockade of their inhibition of DC maturation, respectively. However, alpha-melanocyte-stimulating hormone and calcitonin gene-related peptide had no demonstrable effect on DC maturation.
Cornea and aqueous humor, principally through transforming growth factor beta(2,) promote generation of phenotypically and functionally immature DCs. Clinical Relevance Our results indicate that relative immune quiescence in the cornea and in the anterior segment is actively maintained in part by the inhibitory effect of transforming growth factor beta(2) on resident DCs and by their suppression of T-cell-mediated immune and inflammatory responses.
确定眼前节（房水和角膜）是否能主动抑制树突状细胞（DC）成熟。
将树突状细胞注射到同基因角膜或结膜中，使用共聚焦显微镜评估其对局部环境反应时表面主要组织相容性复合体II类分子的表达。将未成熟DC与角膜上清液或房水共培养，以评估它们对DC表型和功能成熟的调节作用。
与结膜注射的DC相比，角膜注射的DC表面主要组织相容性复合体II类分子的表达上调受到抑制。角膜上清液处理和房水处理的DC保持未成熟状态，表现为高抗原摄取但共刺激分子（CD80和CD86）表达低以及T细胞刺激能力差。用抗转化生长因子β2处理房水和角膜上清液，分别导致其对DC成熟抑制的完全和部分阻断。然而，α-黑素细胞刺激素和降钙素基因相关肽对DC成熟无明显作用。
角膜和房水主要通过转化生长因子β2促进表型和功能上未成熟DC的生成。临床意义我们的结果表明，角膜和眼前节相对的免疫静止状态部分是通过转化生长因子β2对驻留DC的抑制作用及其对T细胞介导的免疫和炎症反应的抑制来积极维持的。
