The Subpopulation of CD4+ CD25+ splenocytes that delays adoptive transfer of diabetes expresses L-selectin and high levels of CCR7
The Subpopulation of CD4+ CD25+ splenocytes that delays adoptive transfer of diabetes expresses L-selectin and high levels of CCR7
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DOI：
10.4049/jimmunol.169.5.2461
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发表时间：
2002-09-01
影响因子：
4.4
通讯作者：
Fathman, CG
中科院分区：
文献类型：
--
作者：
Szanya, V;Ermann, J;Fathman, CG
最近，CD 4（+）CD 25（+）T细胞与糖尿病的控制有关，这表明糖尿病前期NOD小鼠炎症的胰岛处于外周免疫监视之下。在此，我们发现CD 4（+）CD 25（+）脾细胞在与胰岛浸润细胞的共转移中抑制糖尿病。此外，CD 62 L表达是体内CD 4（+）CD 25（+）细胞的疾病延迟效应所必需的，但不是体外抑制功能所必需的。我们证明，CD 4（+）CD 25（+）CD 62 L（+）脾细胞高水平表达CCR 7，并向次级淋巴组织趋化因子和ELC（巨噬细胞炎性蛋白-3 β）、淋巴趋化因子迁移，而CD 4（+）CD 25（+）CD 62 L（-）脾细胞优先表达CCR 2、CCR 4和CXCR 3，并向相应的炎性趋化因子迁移。这些数据表明，CD 4（+）CD 25（+）CD 62 L（+），而不是CD 4（+）CD 25（+）CD 62 L（-），脾细胞延迟糖尿病转移，和CD 4（+）CD 25（+）抑制性T细胞是由至少两个亚群，表现出不同的体内共转移和表达不同的趋化因子受体和趋化反应谱，尽管在体外表现出等效的抑制功能。
Recently, CD4(+)CD25(+) T cells have been implicated in the control of diabetes, suggesting that the inflamed islets of Langerhans in prediabetic NOD mice are under peripheral immune surveillance. Here we show that CD4(+)CD25(+) splenocytes inhibit diabetes in cotransfer with islet-infiltrating cells. Furthermore, CD62L expression is necessary for this disease-delaying effect of CD4(+)CD25(+) cells in vivo, but not for their suppressor function in vitro. We demonstrate that the CD4(+)CD25(+)CD62L(+) splenocytes express CCR7 at high levels and migrate toward secondary lymphoid tissue chemokine and ELC (macrophage-inflammatory protein-3beta), lymphoid chemokines, whereas CD4(+)CD25(+)CD62L(-) splenocytes preferentially express CCR2, CCR4, and CXCR3 and migrate toward the corresponding inflammatory chemokines. These data demonstrate that CD4(+)CD25(+)CD62L(+), but not CD4(+)CD25(+)CD62L(-), splenocytes delay diabetes transfer, and that CD4(+)CD25(+) suppressor T cells are comprised of at least two subpopulations that behave differently in cotransfer in vivo and express distinct chemokine receptor and chemotactic response profiles despite demonstrating equivalent suppressor functions in vitro.