Preferential migration of T regulatory cells induced by IL-16
Preferential migration of T regulatory cells induced by IL-16
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DOI：
10.4049/jimmunol.179.10.6439
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发表时间：
2007-11-15
影响因子：
4.4
通讯作者：
Cruikshank, William
中科院分区：
文献类型：
--
作者：
McFadden, Caroline;Morgan, Ross;Cruikshank, William
作为CD 4的天然配体，IL-16已被证明优先诱导Th 1细胞的迁移，并且在与IL-2的长期培养中，IL-16促进CD 4（+）CD 25（+）细胞的扩增。此外，IL-16在哮喘炎症中具有免疫调节作用，因为外源性给药显著降低炎症和气道高反应性。然而，其机制尚不清楚。基于其功能特性和潜在的免疫调节作用，我们研究了IL-16募集和影响调节性T细胞（Treg）发育的能力。我们现在证明IL-16优先诱导CD 25（+）CTLA-4（+）人T细胞亚群的迁移，并且应答细胞产生IFN γ和TGF β，但不产生IL-10。这些细胞对抗原刺激相对无反应，并且可以抑制自体T细胞的增殖和IL-5产生，但不能抑制IFN γ产生。我们进一步证明了IL-16募集的细胞富含叉头盒P3（Foxp 3）。此外，我们发现IL-16刺激可能有助于Foxp 3（+）Treg细胞的从头诱导，因为FoxP 3阴性T细胞刺激48 h导致FoxP 3 mRNA和蛋白的表达。这些数据表明，在炎症部位，IL-16可能通过优先诱导现有Treg细胞的迁移反应以及诱导FoxP 3（+）细胞的从头产生而有助于选择性Treg细胞扩增。这些发现为IL-16在Th 2介导的炎症中的免疫抑制作用提供了潜在的机制。
As a natural ligand for CD4, IL-16 has been shown to preferentially induce migration in Th1 cells, and, in long-term cultures with IL-2, IL-16 facilitates the expansion of CD4(+)CD25(+) cells. In addition, IL-16 has an immunomodulatory role in asthmatic inflammation, as exogenous administration significantly reduces inflammation and airway hyperreactivity. The mechanism for this, however, is not clear. Based on its functional characteristics and potential immunomodulatory role, we investigated the ability of IL-16 to recruit and influence the development of T regulatory (Treg) cells. We now demonstrate that IL-16 preferentially induces migration in a CD25(+)CTLA-4(+) human T cell subset and that responding cells produce IFN gamma and TGF beta but not IL-10. These cells are relatively unresponsive to antigenic stimulation and can suppress proliferation and IL-5, but not IFN gamma, production by autologous T cells. We further demonstrate that IL-16-recruited cells are enriched for Forkhead box P3 (Foxp3). In addition, we find that IL-16 stimulation may facilitate de novo induction of Foxp3(+) Treg cells, because the stimulation of FoxP3-negative T cells for 48 h results in the expression of FoxP3 mRNA and protein. These data indicate that at sites of inflammation IL-16 may contribute to selective Treg cell expansion through the preferential induction of a migratory response from existing Treg cells, as well as by the induction of de novo generation of FoxP3(+) cells. These findings offer a potential mechanism for the immunosuppressive effects of IL-16 seen in Th2-mediated inflammation.