The Transcription Factor Hobit Identifies Human Cytotoxic CD4(+) T Cells.
The Transcription Factor Hobit Identifies Human Cytotoxic CD4(+) T Cells.
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DOI：
10.3389/fimmu.2017.00325
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发表时间：
2017
影响因子：
7.3
通讯作者：
Hombrink P
中科院分区：
文献类型：
--
作者：
Oja AE;Vieira Braga FA;Remmerswaal EB;Kragten NA;Hertoghs KM;Zuo J;Moss PA;van Lier RA;van Gisbergen KP;Hombrink P
T细胞谱系通常分为表达CD 4的辅助性T细胞和表达CD 8的细胞毒性T细胞，所述辅助性T细胞通过细胞因子分泌来抑制免疫应答，所述细胞毒性T细胞通过释放细胞毒性分子来消除受感染的靶细胞。最近，符合细胞毒性CD 8 + T细胞表型的CD 4 + T细胞群体已得到越来越多的认可。这些细胞毒性CD 4 + T细胞在蛋白质水平上显示颗粒酶B和穿孔素的组成型表达，并介导靶细胞的HLA II类依赖性杀伤。在人类中，这种细胞毒性特征存在于人巨细胞病毒（hCMV）特异性的CD 4 + T细胞群中，但不存在于流感病毒或EB病毒特异性的CD 4 + T细胞群中，这表明，特别是hCMV感染诱导细胞毒性CD 4 + T细胞的形成。我们先前已经描述了T细胞中Blimp-1的转录因子同源物（Hobit）在hCMV感染后产生的CD 45 RA+效应CD 8 + T细胞中特异性上调。在这里，我们描述了Hobit在人CD 4 + T细胞中的表达模式。我们发现Hobit在细胞毒性CD 4 + T细胞中表达，并且在初次hCMV感染后Hobit+ CD 4 + T细胞积累。Hobit+ CD 4 + T细胞显示出与Hobit+ CD 8 + T细胞高度重叠的特征，包括细胞毒性分子、T-bet和CX 3CR 1的表达。有趣的是，hCMV感染后产生的γδ+ T细胞也上调Hobit表达，并显示出与细胞毒性CD 4+和CD 8 + T细胞相似的效应表型。这些发现表明，CD 4+、CD 8+和γδ+ T细胞中存在一种共同的分化途径，可能涉及霍比特人驱动的长寿命细胞毒性效应子功能的获得。
The T cell lineage is commonly divided into CD4-expressing helper T cells that polarize immune responses through cytokine secretion and CD8-expressing cytotoxic T cells that eliminate infected target cells by virtue of the release of cytotoxic molecules. Recently, a population of CD4+ T cells that conforms to the phenotype of cytotoxic CD8+ T cells has received increased recognition. These cytotoxic CD4+ T cells display constitutive expression of granzyme B and perforin at the protein level and mediate HLA class II-dependent killing of target cells. In humans, this cytotoxic profile is found within the human cytomegalovirus (hCMV)-specific, but not within the influenza- or Epstein–Barr virus-specific CD4+ T cell populations, suggesting that, in particular, hCMV infection induces the formation of cytotoxic CD4+ T cells. We have previously described that the transcription factor Homolog of Blimp-1 in T cells (Hobit) is specifically upregulated in CD45RA+ effector CD8+ T cells that arise after hCMV infection. Here, we describe the expression pattern of Hobit in human CD4+ T cells. We found Hobit expression in cytotoxic CD4+ T cells and accumulation of Hobit+ CD4+ T cells after primary hCMV infection. The Hobit+ CD4+ T cells displayed highly overlapping characteristics with Hobit+ CD8+ T cells, including the expression of cytotoxic molecules, T-bet, and CX3CR1. Interestingly, γδ+ T cells that arise after hCMV infection also upregulate Hobit expression and display a similar effector phenotype as cytotoxic CD4+ and CD8+ T cells. These findings suggest a shared differentiation pathway in CD4+, CD8+, and γδ+ T cells that may involve Hobit-driven acquisition of long-lived cytotoxic effector function.