Recruitment and activation of macrophages by pathogenic CD4 T cells in type 1 diabetes: Evidence for involvement of CCR8 and CCL1
Recruitment and activation of macrophages by pathogenic CD4 T cells in type 1 diabetes: Evidence for involvement of CCR8 and CCL1
复制标题
DOI：
10.4049/jimmunol.179.9.5760
复制
发表时间：
2007-11-01
影响因子：
4.4
通讯作者：
Haskins, Kathryn
中科院分区：
文献类型：
--
作者：
Cantor, Joseph;Haskins, Kathryn
将致糖尿病性CD 4 Th 1 T细胞克隆连续转移到年轻NOD或NOD.scid受体中可迅速诱导糖尿病发作，并提供了一个分析胰腺浸润的系统。虽然许多报告表明巨噬细胞在炎症反应中的作用，但很少直接表征胰腺中的巨噬细胞活性。我们先前表明，在迁移到胰腺后，致糖尿病的CD 4 T细胞克隆产生多种炎性细胞因子和趋化因子，导致巨噬细胞的募集。在这项研究中，我们研究了巨噬细胞被T细胞招募和激活的机制。通过致糖尿病T细胞克隆BDC-2.5过继转移后的浸润细胞分析表明，大量F4/80和CD 11b染色的细胞被募集到胰腺中，在胰腺中它们被激活以产生IL-1 β、TNF-α和NO，并表达趋化因子受体CCR 5、CXCR 3和CCR 8。致糖尿病性CD 4 T细胞克隆在体外产生几种炎性趋化因子，但在过继转移后，我们发现唯一能在体外检测到的趋化因子是CCL 1。这些结果提供了第一个证据表明，CCR 8/CCL 1相互作用可能通过巨噬细胞募集和激活在1型糖尿病中发挥作用。
Adoptive transfer of diabetogenic CD4 Th1 T cell clones into young NOD or NOD.scid recipients rapidly induces onset of diabetes and also provides a system for analysis of the pancreatic infiltrate. Although many reports have suggested a role for macrophages in the inflammatory response, there has been little direct characterization of macrophage activity in the pancreas. We showed previously that after migration to the pancreas, diabetogenic CD4 T cell clones produce a variety of inflammatory cytokines and chemokines, resulting in the recruitment of macrophages. In this study, we investigated mechanisms by which macrophages are recruited and activated by T cells. Analysis of infiltrating cells after adoptive transfer by the diabetogenic T cell clone BDC-2.5 indicates that large numbers of cells staining for both F4/80 and CD11b are recruited into the pancreas where they are activated to make IL-1 beta, TNF-alpha, and NO, and express the chemokine receptors CCR5, CXCR3, and CCR8. Diabetogenic CD4 T cell clones produce several inflammatory chemokines in vitro, but after adoptive transfer we found that the only chemokine that could be detected ex vivo was CCL1. These results provide the first evidence that CCR8/CCL1 interaction may play a role in type 1 diabetes through macrophage recruitment and activation.