Expression of CD103 identifies human regulatory T-cell subsets
Expression of CD103 identifies human regulatory T-cell subsets
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DOI：
10.1016/j.jaci.2006.07.034
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发表时间：
2006-12-01
影响因子：
14.2
通讯作者：
Delespesse, Guy
中科院分区：
文献类型：
--
作者：
Allakhverdi, Zoulfia;Fitzpatrick, David;Delespesse, Guy
背景：由于缺乏特异性表面标记物，对人类疾病中自然发生的T调节性CD4(+) （nTreg）细胞的分析受到阻碍。事实上，通常用于识别nTreg细胞的CD25抗原也在活化的效应T细胞上表达。目的：我们试图检测携带CD103的CD4(+) T细胞是否是抑制细胞，而不考虑CD25的共表达。方法：我们首先比较了新分离的扁桃体CD103(+)CD25（-）细胞与CD103(-)CD25（高）细胞抑制t细胞反应和FoxP3 mRNA表达的能力。然后用同种异体树突状细胞刺激新生儿或成人CD4(+) T细胞诱导CD103，并比较CD103（+）和CD103（-）部分。结果：扁桃体CD4(+)CD103(+)CD25(-) T细胞表现出与CD103(-)CD25（高）T细胞相当的抑制活性，并且含有相似量的FoxP3 mRNA。体外生成的同种异体抗原诱导的CD103+细胞共表达CD25，抑制t细胞活化，并且比从相同培养中分离的CD103(-)CD25（+）细胞含有更多的FoxP3 mRNA。最后，新生儿的同种异体反应细胞比成人的同种异体细胞含有更多的CD103(+) Treg细胞，并且与后者不同，对启动异体抗原的反应降低。结论：检测CD103和CD25共表达可以识别3个人类CD4(+) nTreg细胞亚群，检测CD4(+) T细胞上的CD103可以识别nTYeg细胞，而不考虑CD25共表达。临床意义：脐带血对CD103（+）抑制细胞的诱导作用更大，这可能与脐带血作为成人骨髓移植的一种成功的临床应用有关。
Background: Analysis of naturally occurring T regulatory CD4(+) (nTreg) cells in human diseases is hampered by the lack of specific surface marker. Indeed, the CD25 antigen, which is typically used to identify nTreg cells, is also expressed on activated effector T cells.Objective: We sought to examine whether CD4(+) T cells bearing CD103 are suppressor cells, regardless of CD25 coexpression.Methods: We first compared freshly isolated tonsillar CD103(+)CD25(-) cells with their CD103(-)CD25(high) counterparts for their capacity to suppress T-cell response and their expression of FoxP3 mRNA. Next CD103 was induced on neonatal or adult CD4(+) T cells stimulated with allogeneic dendritic cells, and the CD103(+) and CD103(-) fractions were compared as above.Results: Tonsillar CD4(+)CD103(+)CD25(-) T cells displayed comparable suppressive activity and contained similar amounts of FoxP3 mRNA as their CD103(-)CD25(high) counterparts. In vitro-generated alloantigen-primed CD103+ cells coexpressed CD25, suppressed T-cell activation, and contained more FoxP3 mRNA than the CD103(-)CD25(+) cells isolated from the same cultures. Finally, neonatal alloreactive cells contained more CD103(+) Treg cells than their adult counterparts and, unlike the latter, became hyporesponsive to the priming alloantigens.Conclusions: The examination of CD103 and CD25 coexpression allows identification of 3 subsets of human CD4(+) nTreg cells, and the detection of CD103 on CD4(+) T cells identifies nTYeg cells, regardless of CD25 coexpression.Clinical implications: The greater induction of CD103(+) suppressor cells by cord blood should be related to its successful clinical use as an alternative to adult bone marrow transplantation.