Bremser Anna, Brack Maria, Izcue Ana
Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany; Centre for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany.
Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany; Centre for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, University of Freiburg, Freiburg, Germany.
PLoS One. 2015 Sep 9;10(9):e0137393. doi: 10.1371/journal.pone.0137393. eCollection 2015.
T lymphocytes elicit specific responses after recognizing cognate antigen. However, antigen-experienced T cells can also respond to non-cognate stimuli, such as cytokines. CD4+ Foxp3+ regulatory T cells (Treg) exhibit an antigen-experienced-like phenotype. Treg can regulate T cell responses in an antigen-specific or bystander way, and it is still unclear as to which extent they rely on T cell receptor (TCR) signals. The study of the antigen response of Treg has been hampered by the lack of downstream readouts for TCR stimuli. Here we assess the effects of TCR signals on the expression of a classical marker of early T cell activation, CD69. Although it can be induced following cytokine exposure, CD69 is commonly used as a readout for antigen response on T cells. We established that upon in vitro TCR stimulation CD69 induction on Foxp3+ Treg cells was more dependent on signaling via soluble factors than on TCR activation. By contrast, expression of the activation marker Nur77 was only induced after TCR stimulation. Our data suggest that Treg are more sensitive to TCR-independent signals than Foxp3- cells, which could contribute to their bystander activity.
T淋巴细胞在识别同源抗原后引发特异性反应。然而，经历过抗原刺激的T细胞也能对非同源刺激作出反应，如细胞因子。CD4+ Foxp3+调节性T细胞（Treg）呈现出一种类似经历过抗原刺激的表型。Treg可以以抗原特异性或旁观者方式调节T细胞反应，它们在多大程度上依赖于T细胞受体（TCR）信号仍不清楚。由于缺乏TCR刺激的下游读数，Treg的抗原反应研究受到了阻碍。在此，我们评估TCR信号对早期T细胞活化经典标志物CD69表达的影响。尽管CD69在细胞因子暴露后可被诱导，但它通常被用作T细胞抗原反应的读数。我们确定，在体外TCR刺激下，Foxp3+ Treg细胞上CD69的诱导更多地依赖于可溶性因子的信号传导，而非TCR激活。相比之下，激活标志物Nur77的表达仅在TCR刺激后被诱导。我们的数据表明，Treg比Foxp3-细胞对TCR非依赖性信号更敏感，这可能有助于它们的旁观者活性。
