Regulatory CD4 T cells control the size of the peripheral activated/memory CD4 T cell compartment

Regulatory CD4 T cells control the size of the peripheral activated/memory CD4 T cell compartment
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DOI:
10.4049/jimmunol.164.7.3573
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发表时间:
2000-04-01
影响因子:
4.4
通讯作者:
Bandeira, A
Bandeira, A
中科院分区:
医学2区
文献类型:
--
作者:
Annacker, O;Burlen-Defranoux, O;Bandeira, A

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迄今为止,导致健康动物外周血中T细胞数量稳定的机制尚未得到很好的理解。我们跟踪了CD 45 RB(高)(初始)和CD 45 RB(低)的扩增。从正常小鼠转移到同基因Rag-2(0/0)受体中的(活化/记忆)CD 4 T细胞以及当两个群体共注射时外周重建的动力学,幼稚细胞获得活化的表型,并显示出依赖于受体所处环境的高增殖能力(无特定病原体vs常规饲养条件)、接受者的年龄和注射组群中CD 45 RB(低)T细胞的存在。CD 45 RB(低)CD 4 T细胞保护宿主免受CD 45 RB(高)CD 4 T细胞诱导的炎症性肠病,并显示出有限程度的扩增。从GF小鼠分离的CD 45 RB(低)CD 4 T细胞也显示出预防炎性肠病的能力,表明至少部分天然调节性T细胞是自身反应性的。结果表明:1)淋巴细胞缺陷型受体中的外周T细胞扩增代表经典的免疫应答,其主要由外源性Ag促进; 2)天然调节性T细胞控制活化/记忆外周CD 4 T细胞区室的大小。
The mechanisms leading to stable T cell numbers in the periphery of a healthy animal are, to date, not well understood. We followed the expansion of CD45RB(high) (naive) and CD45RB(low) (activated/memory) CD4 T cells transferred from normal mice into syngeneic Rag-2(0/0) recipients and the dynamics of peripheral reconstitution when both populations were coinjected, Naive cells acquired an activated phenotype and showed a high proliferative capacity that was dependent on the environment in which the recipients were kept (specific pathogen-free vs conventional housing conditions), the age of the recipients, and the presence of CD45RB(low) T cells in the injected cohort. CD45RB(low) CD4 T cells protected the host from CD45RB(high) CD4 T cell-induced inflammatory bowel disease and showed a limited degree of expansion. CD45RB(low) CD4 T cells isolated from GF mice also showed the ability to prevent inflammatory bowel disease, indicating that at least part of the natural regulatory T cells are self-reactive. The results indicate that 1) peripheral T cell expansion in lymphocyte-deficient recipients represent classical immune responses, which are mainly promoted by exogenous Ags and 2) natural regulatory T cells control the size of the activated/memory peripheral CD4 T cell compartment.