Mazerolles Fabienne, Rieux-Laucat Frédéric
INSERM UMR1163, Laboratory of Immunogenetics of Paediatric Autoimmunity, Paris, France; Paris Descartes - Sorbonne Paris Cité University, Imagine Institute Paris, France.
INSERM UMR1163, Laboratory of Immunogenetics of Paediatric Autoimmunity, Paris, France; Paris Descartes - Sorbonne Paris Cité University, Imagine Institute Paris, France.
J Immunol Methods. 2024 Dec;535:113775. doi: 10.1016/j.jim.2024.113775. Epub 2024 Nov 14.
We have shown in previous studies that naive CD4 T cells isolated from human peripheral blood are induced to proliferate by CD4CD11cCD14CD16 dendritic cells presenting the superantigen SEE. Since this population is very poorly expressed in blood, we tried to find other antigen presenting cells (APCs) to induce this proliferation. The aim of the previous studies was to investigate the regulation of T cell proliferation in pediatric monogenic autoimmune diseases and the regulation of this proliferation by regulatory T cells (TREGs). Since the blood samples from pediatric patients were very small, it was important to study other APCs that are more commonly present in the blood. In this study we tested different APCs isolated from controls, CD19 B cells, CD11cCD14 and CD11cCD14 monocytes, CD11cCD14CD16 and CD16 dendritic cells. The different T cell populations, naive effector T cells and regulatory T cells were separated simultaneously from the same sample. We show in these studies that CD19 B cells, CD14 and more specifically CD14CD16, are also able to induce T cell proliferation as previously described with CD14CD16 DCs, but under different conditions. No proliferation was induced with CD14 monocytes. However, these three APCs are less potent than CD16 and inhibition by TREG is more difficult to detect. In addition, when we test the role of CTLA-4 in the regulation of TEFF proliferation, we observe that for some APCs, the inhibition by CTLA-4 was quite different. No inhibition was observed with CD19 B cells in contrast to CD11cCD14CD16 and CD11cCD14CD16.
我们在之前的研究中表明，从人外周血中分离出的初始CD4 T细胞可被呈递超抗原SEE的CD4CD11cCD14CD16树突状细胞诱导增殖。由于该细胞群体在血液中的表达非常低，我们试图寻找其他抗原呈递细胞（APC）来诱导这种增殖。之前研究的目的是调查小儿单基因自身免疫性疾病中T细胞增殖的调控以及调节性T细胞（TREG）对这种增殖的调控。由于小儿患者的血样非常少，研究血液中更常见的其他APC很重要。在本研究中，我们测试了从对照中分离出的不同APC，CD19 B细胞、CD11cCD14和CD11cCD14单核细胞、CD11cCD14CD16和CD16树突状细胞。不同的T细胞群体，即初始效应T细胞和调节性T细胞，是从同一样本中同时分离出来的。我们在这些研究中表明，CD19 B细胞、CD14以及更具体的CD14CD16，也能够如之前用CD14CD16 DC所描述的那样诱导T细胞增殖，但条件不同。CD14单核细胞未诱导增殖。然而，这三种APC的效力低于CD16，并且TREG的抑制作用更难检测到。此外，当我们测试CTLA-4在调节TEFF增殖中的作用时，我们观察到对于某些APC，CTLA-4的抑制作用差异很大。与CD11cCD14CD16和CD11cCD14CD16相反，CD19 B细胞未观察到抑制作用。
