天然存在的肺CD4(+)CD25(+)调节性T细胞的激活需要CD8与MHC I相互作用。
Activation of naturally occurring lung CD4(+)CD25(+) regulatory T cells requires CD8 and MHC I interaction.
作者信息
Joetham Anthony, Takeda Katsuyuki, Miyahara Nobuaki, Matsubara Shigeki, Ohnishi Hiroshi, Koya Toshiyuki, Dakhama Azzeddine, Gelfand Erwin W
机构信息
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA.
出版信息
Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15057-62. doi: 10.1073/pnas.0706765104. Epub 2007 Sep 12.
Naturally occurring Foxp3(+)CD4(+)CD25(+) T cells (nTregs) isolated from lungs of naive mice regulate allergic airway hyperresponsiveness (AHR) and inflammation. Here, we demonstrate the critical requirement for engagement of MHC class I on CD4(+)CD25(+) T cells by CD8 for the functional activation of these nTregs. Suppression of allergen-induced AHR and inflammation by nTregs was abolished in mice treated with anti-CD8. Correspondingly, decreased levels of IL-10 and TGF-beta and increased levels of Th2 cytokines in bronchoalveolar lavage were detected in these treated mice. Similarly, nTregs isolated from beta2m(-/-) mice or from mice treated with anti-MHC I antibody in vitro before intratracheal transfer failed to modulate AHR or inflammation. Coculture of nTregs with CD8(+) T cells increased IL-10 and TGF-beta. Addition of anti-MHC I or anti-CD8 reduced IL-10 and TGF-beta. These results demonstrate that functional activation of nTregs requires the interaction between MHC I on CD4(+)CD25(+) T cells and CD8.
从未接触过抗原的小鼠肺中分离出的天然存在的叉头状转录因子3（Foxp3）阳性CD4阳性CD25阳性T细胞（nTregs）可调节过敏性气道高反应性（AHR）和炎症。在此，我们证明了CD8与CD4阳性CD25阳性T细胞上的MHC I类分子结合对于这些nTregs的功能激活至关重要。在用抗CD8抗体处理的小鼠中，nTregs对变应原诱导的AHR和炎症的抑制作用被消除。相应地，在这些处理过的小鼠的支气管肺泡灌洗中检测到IL-10和转化生长因子-β（TGF-β）水平降低，以及Th2细胞因子水平升高。同样，从β2微球蛋白（β2m）基因敲除小鼠或在气管内转移前体外经抗MHC I抗体处理的小鼠中分离出的nTregs无法调节AHR或炎症。nTregs与CD8阳性T细胞共培养可增加IL-10和TGF-β。添加抗MHC I或抗CD8可降低IL-10和TGF-β。这些结果表明，nTregs的功能激活需要CD4阳性CD25阳性T细胞上的MHC I与CD8之间的相互作用。
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